左卡尼汀及其酰化物在中国健康志愿者体内的药代动力学研究
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摘要
目的:建立专属、灵敏、简便的检测人血浆和尿液中左卡尼汀(L-carnitine,LC)及其酰化物乙酰左卡尼汀(Acetyl-L-cainitine,ALC)、丙酰左卡尼汀(Propionyl-L-cainitine,PLC)含量的高效液相色谱方法,并应用于中国健康人左卡尼汀口服液单次给药后左卡尼汀及其酰化物的人体药代动力学研究。
方法:HPLC-UV法:血浆样本经蛋白沉淀处理后,用对-溴苯甲酰甲基溴化物(PBPB)将样本紫外衍生化,高效液相色谱法测定,采用Hypersil SiO2色谱柱(4.6×250mm;5μm),流动相为乙腈:柠檬酸缓冲液(10:90),流速1.2ml·min~(-1),检测波长260nm。HPLC-FL法:血浆样本经蛋白沉淀处理后,用1-氨基蒽(1-AA)将样本荧光衍生化,高效液相色谱方法测定,色谱柱采用Hypersil C_(18)柱(4.6mm×200mm,5μm),流动相为乙腈-0.1mol·L~(-1)乙酸铵(34:66),流速为1.0ml·min~(-1),检测波长:Ex248nm,Em418nm。绘制标准曲线,测定精密度、回收率和稳定性,检测正常人血浆及尿液的左卡尼汀及其酰化物的含量。12名健康受试者左卡尼汀口服液单次给药2g后,分别于服药前(0h)和服药后0.5h,1.0h,1.5h,2h,2.5h,3.0h,3.5h,4.0h,5.0h,6.0h,8.0h,12.0h,24.0h,取前臂静脉血4ml,置肝素试管中,3000r·min~(-1)离心,分离血浆,同时收集给药后0h,0～2h,2～4h,4～8h,8～12h,12～24 h的尿液,-20℃冷冻待测。采用荧光衍生化高效液相色谱法测定血浆和尿中LC,ALC,PLC的含量。采用DAS软件进行处理,计算药代动力学参数。
结果:紫外高效液相色谱法的血浆LC线性范围为2.5～500μmol·L~(-1),尿液LC的线性范围为2～1000μmol·L~(-1),回收率、精密度及稳定性试验均符合血、尿检测方法学的要求。荧光高效液相色谱法的血浆和尿液LC、ALC和PLC样品的线性范围分别是2.5～500,0.5～50,0.1～20μmol·L~(-1)和2～1000,1～500,0.2～50μmol·L~(-1)。回收率、精密度及稳定性试验均符合血、尿检测方法学的要求。采用荧光高效液相色谱法对12名中国健康受试者左卡尼汀口服液单次给药2g后左卡尼汀及酰化物进行药代动力学研究,主要药代动力学参数LC:Cmax:(84.73±25.23)μmol·L~(-1),t_(1/2α):(1.66±1.20)h,t_(1/2β):(60.33±14.97)h,AUC_((0-t)):(2676.41±708.33)μmol·L~(-1)·h,AUC_((0-∞)):(2676.41±708.33)μmol·L~(-1)·h,Tmax:(3.4±0.46)h。ALC:t_(1/2α):(6.33±6.39)h,t_(1/2β)(5.90±28.86)h,AUC_((0-t)):(119.54±55.84)μmol·L~(-1)·h,AUC_((0-∞)):(166.20±77.41)μmol·L~(-1)·h,Tmax:(4±0.66)h,Cmax:(12.89±5.52)μmol·L~(-1)和PLC:t_(1/2α):(3.10±3.93)h,t_(1/2β):(25.74±30.33)h,AUC_((0-t)):(57.98±48.52)μmol·L~(-1)·h,AUC_((0-∞)):(155.57±264.22)μmol·L~(-1)·h,Tmax:(3.8±0.79)h,Cmax.(5.08±3.08)μmol·L~(-1)。LC、ALC、PLC 24小时尿药累计排泄量分别为:(613.47±161.72)μmol,(368.25±134.77)μmol,(61.29±37.75)μmol,LC24小时累计排泄率为6.05%。
结论:建立了同时检测血浆和尿液中左卡尼汀浓度的紫外衍生化高效液相色谱法和同时检测血浆和尿液中左卡尼汀及酰化物的荧光衍生化高效液相色谱法。采用荧光衍生化高效液相色谱法,首次测定了12名中国健康受试者左卡尼汀口服液单次给药2g后左卡尼汀及酰化物的药代动力学参数。
Subject:To develop specific,sensitive and simple HPLC methods to determine L-carnitine(LC) and its acyl esters Acetyl-L-cainitine(ALC) and Propionyl-L-cainitine(PLC) levels in human plasma and urine.And HPLC method was used in pharmacokinetic study of L-carnitine and its acyl esters after single oral administration of L-carnitine oral solution in Chinese healthy volunteers.
METHODS HPLC-UV:The analytes were extracted by protein precipitation and then precolumn derivatization with 2,4'-Dibromoacetophenone(PBPB) were performed. The fluorescent derivatives were separated on a Hypersil SiO_2 column,and the mobile phase consisted of acetonitrile-citrate buffer solution(10:90),the flow rate was 1.2 ml·min~(-1),the derivatives were monitored with a UV detector set at 260nm.HPLC-FL:The analytes were extracted by protein precipitation and then precolumn derivatization with 1-aminoanthracene(1-AA) were performed.The fluorescent derivatives were separated on a Hypersil C_(18) column,and the mobile phase consisted of acetonitrile-0.1mol·L~(-1) ammonium acetate(34:66),the flow rate was 1.0ml·min~(-1).The derivatives were monitored with a fluorimetric detector set at 248 nm(excitation wavelength) and 418 nm(emission wavelength).
After single oral administration of 2g L-carnitine oral solution in 12 Chinese healthy volunteers,the plasma was collected at Oh,0.5h,1.0h,1.5h,2h,2.5h,3.0h,3.5h,4.0h,5.0h, 6.0h,8.0h,12.0h,24.0h,and the urine was collected at Oh,0～2h,2～4h,4～8h,8～12h, 12～24h.The concentration of LC,ALC and PLC in plasma and urine were measured by HPLC-FL and the pharmacokinetics parameters were calculated by DAS software.
RESULT:The good linearity of the assay were observed over the concentration ranges investigated,2.5～500μmol·L~(-1) in plasma and 2～1000μmol·L~(-1) in urine for LC by HPLC-UV and 2～500μmol·L~(-1) for LC,0.5～50μmol·L~(-1) for ALC,0.1～20μmol·L~(-1) for PLC in plasma and 2～1000μmol·L~(-1) for LC,1～500μmol·L~(-1) for ALC,0.2～50μmol·L~(-1) for PLC in urine by HPLC-FL.The recoveries,precision and stability test of LC,ALC and PLC correspond the requirement in plasma and urine.The methods were proved to be stable,accurate and convenient to study the concentrations of LC,ALC and PLC in clinical plasma and urine.After single oral administration of 2g L-carnitine oral solution, the main pharmacokinetic parameter of LC Cmax is(84.73+25.23)μmol·L~(-1),t_(1/2β) is (60.33+14.97)h,AUC_((0-t)) is(2676.41+708.33)μmol·L~(-1)·h,Tmax is(3.4+0.46)h.ALC: t_(1/2α):(6.33+6.39)h,t_(1/2β):(35.90±28.86)h,AUC_((0-t)):119.54±55.84μmol·L~(-1)·h,AUC_((0-∞)): 166.20±77.41μmol·L~(-1)·h,Tmax:(2.4±0.66)h,Cmax:(12.89±5.52)μmol·L~(-1),and PLC:t_(1/2α):(3.10±3.93)h,t_(1/2β)::(25.74±30.33)h,AUC_((0-t)):(57.98±48.52)μmol·L~(-1)·h, AUC_((0-∞)):(155.57±264.22)μmol·L~(-1)·h,Tmax:(3.8±0.79)h,Cmax:(5.08±3.08)μmol·L~(-1). The accumulated excretion of LC,ALC and PLC were(613.47±161.72)μmol, (368.25±134.77)μmol,(61.29±37.75)μmol in 24h,respectively and the accumulated excretion rate of LC was 6.05%in 24h after administration.
CONCLUSION:The specific,sensitive and simple HPLC-UV and HPLC-FL methods were developed to determine L-carnitine(LC) and its acyl esters Acetyl-L-cainitine(ALC) and Propionyl-L-cainitine(PLC) levels in human plasma and urine.The HPLC-FL method was successfully used in pharmacokinetic study of L-carnitine and its acyl esters after single oral administration of L-carnitine oral solution in Chinese healthy volunteers.
方法:HPLC-UV法:血浆样本经蛋白沉淀处理后,用对-溴苯甲酰甲基溴化物(PBPB)将样本紫外衍生化,高效液相色谱法测定,采用Hypersil SiO2色谱柱(4.6×250mm;5μm),流动相为乙腈:柠檬酸缓冲液(10:90),流速1.2ml·min~(-1),检测波长260nm。HPLC-FL法:血浆样本经蛋白沉淀处理后,用1-氨基蒽(1-AA)将样本荧光衍生化,高效液相色谱方法测定,色谱柱采用Hypersil C_(18)柱(4.6mm×200mm,5μm),流动相为乙腈-0.1mol·L~(-1)乙酸铵(34:66),流速为1.0ml·min~(-1),检测波长:Ex248nm,Em418nm。绘制标准曲线,测定精密度、回收率和稳定性,检测正常人血浆及尿液的左卡尼汀及其酰化物的含量。12名健康受试者左卡尼汀口服液单次给药2g后,分别于服药前(0h)和服药后0.5h,1.0h,1.5h,2h,2.5h,3.0h,3.5h,4.0h,5.0h,6.0h,8.0h,12.0h,24.0h,取前臂静脉血4ml,置肝素试管中,3000r·min~(-1)离心,分离血浆,同时收集给药后0h,0～2h,2～4h,4～8h,8～12h,12～24 h的尿液,-20℃冷冻待测。采用荧光衍生化高效液相色谱法测定血浆和尿中LC,ALC,PLC的含量。采用DAS软件进行处理,计算药代动力学参数。
结果:紫外高效液相色谱法的血浆LC线性范围为2.5～500μmol·L~(-1),尿液LC的线性范围为2～1000μmol·L~(-1),回收率、精密度及稳定性试验均符合血、尿检测方法学的要求。荧光高效液相色谱法的血浆和尿液LC、ALC和PLC样品的线性范围分别是2.5～500,0.5～50,0.1～20μmol·L~(-1)和2～1000,1～500,0.2～50μmol·L~(-1)。回收率、精密度及稳定性试验均符合血、尿检测方法学的要求。采用荧光高效液相色谱法对12名中国健康受试者左卡尼汀口服液单次给药2g后左卡尼汀及酰化物进行药代动力学研究,主要药代动力学参数LC:Cmax:(84.73±25.23)μmol·L~(-1),t_(1/2α):(1.66±1.20)h,t_(1/2β):(60.33±14.97)h,AUC_((0-t)):(2676.41±708.33)μmol·L~(-1)·h,AUC_((0-∞)):(2676.41±708.33)μmol·L~(-1)·h,Tmax:(3.4±0.46)h。ALC:t_(1/2α):(6.33±6.39)h,t_(1/2β)(5.90±28.86)h,AUC_((0-t)):(119.54±55.84)μmol·L~(-1)·h,AUC_((0-∞)):(166.20±77.41)μmol·L~(-1)·h,Tmax:(4±0.66)h,Cmax:(12.89±5.52)μmol·L~(-1)和PLC:t_(1/2α):(3.10±3.93)h,t_(1/2β):(25.74±30.33)h,AUC_((0-t)):(57.98±48.52)μmol·L~(-1)·h,AUC_((0-∞)):(155.57±264.22)μmol·L~(-1)·h,Tmax:(3.8±0.79)h,Cmax.(5.08±3.08)μmol·L~(-1)。LC、ALC、PLC 24小时尿药累计排泄量分别为:(613.47±161.72)μmol,(368.25±134.77)μmol,(61.29±37.75)μmol,LC24小时累计排泄率为6.05%。
结论:建立了同时检测血浆和尿液中左卡尼汀浓度的紫外衍生化高效液相色谱法和同时检测血浆和尿液中左卡尼汀及酰化物的荧光衍生化高效液相色谱法。采用荧光衍生化高效液相色谱法,首次测定了12名中国健康受试者左卡尼汀口服液单次给药2g后左卡尼汀及酰化物的药代动力学参数。
Subject:To develop specific,sensitive and simple HPLC methods to determine L-carnitine(LC) and its acyl esters Acetyl-L-cainitine(ALC) and Propionyl-L-cainitine(PLC) levels in human plasma and urine.And HPLC method was used in pharmacokinetic study of L-carnitine and its acyl esters after single oral administration of L-carnitine oral solution in Chinese healthy volunteers.
METHODS HPLC-UV:The analytes were extracted by protein precipitation and then precolumn derivatization with 2,4'-Dibromoacetophenone(PBPB) were performed. The fluorescent derivatives were separated on a Hypersil SiO_2 column,and the mobile phase consisted of acetonitrile-citrate buffer solution(10:90),the flow rate was 1.2 ml·min~(-1),the derivatives were monitored with a UV detector set at 260nm.HPLC-FL:The analytes were extracted by protein precipitation and then precolumn derivatization with 1-aminoanthracene(1-AA) were performed.The fluorescent derivatives were separated on a Hypersil C_(18) column,and the mobile phase consisted of acetonitrile-0.1mol·L~(-1) ammonium acetate(34:66),the flow rate was 1.0ml·min~(-1).The derivatives were monitored with a fluorimetric detector set at 248 nm(excitation wavelength) and 418 nm(emission wavelength).
After single oral administration of 2g L-carnitine oral solution in 12 Chinese healthy volunteers,the plasma was collected at Oh,0.5h,1.0h,1.5h,2h,2.5h,3.0h,3.5h,4.0h,5.0h, 6.0h,8.0h,12.0h,24.0h,and the urine was collected at Oh,0～2h,2～4h,4～8h,8～12h, 12～24h.The concentration of LC,ALC and PLC in plasma and urine were measured by HPLC-FL and the pharmacokinetics parameters were calculated by DAS software.
RESULT:The good linearity of the assay were observed over the concentration ranges investigated,2.5～500μmol·L~(-1) in plasma and 2～1000μmol·L~(-1) in urine for LC by HPLC-UV and 2～500μmol·L~(-1) for LC,0.5～50μmol·L~(-1) for ALC,0.1～20μmol·L~(-1) for PLC in plasma and 2～1000μmol·L~(-1) for LC,1～500μmol·L~(-1) for ALC,0.2～50μmol·L~(-1) for PLC in urine by HPLC-FL.The recoveries,precision and stability test of LC,ALC and PLC correspond the requirement in plasma and urine.The methods were proved to be stable,accurate and convenient to study the concentrations of LC,ALC and PLC in clinical plasma and urine.After single oral administration of 2g L-carnitine oral solution, the main pharmacokinetic parameter of LC Cmax is(84.73+25.23)μmol·L~(-1),t_(1/2β) is (60.33+14.97)h,AUC_((0-t)) is(2676.41+708.33)μmol·L~(-1)·h,Tmax is(3.4+0.46)h.ALC: t_(1/2α):(6.33+6.39)h,t_(1/2β):(35.90±28.86)h,AUC_((0-t)):119.54±55.84μmol·L~(-1)·h,AUC_((0-∞)): 166.20±77.41μmol·L~(-1)·h,Tmax:(2.4±0.66)h,Cmax:(12.89±5.52)μmol·L~(-1),and PLC:t_(1/2α):(3.10±3.93)h,t_(1/2β)::(25.74±30.33)h,AUC_((0-t)):(57.98±48.52)μmol·L~(-1)·h, AUC_((0-∞)):(155.57±264.22)μmol·L~(-1)·h,Tmax:(3.8±0.79)h,Cmax:(5.08±3.08)μmol·L~(-1). The accumulated excretion of LC,ALC and PLC were(613.47±161.72)μmol, (368.25±134.77)μmol,(61.29±37.75)μmol in 24h,respectively and the accumulated excretion rate of LC was 6.05%in 24h after administration.
CONCLUSION:The specific,sensitive and simple HPLC-UV and HPLC-FL methods were developed to determine L-carnitine(LC) and its acyl esters Acetyl-L-cainitine(ALC) and Propionyl-L-cainitine(PLC) levels in human plasma and urine.The HPLC-FL method was successfully used in pharmacokinetic study of L-carnitine and its acyl esters after single oral administration of L-carnitine oral solution in Chinese healthy volunteers.
引文
[1]J Kerner,C Hoppel.Generic disorders of carnitine metabolism and their nutritional management [J].Annu Rev Nutr,1998,18:179-206
[2]Reda E,Iddio D,Nicolai R,et al.The carnitine system and body composition[J].Acta Diabetol,2003,40(1):106-113
[3]Mario M,Guido B,Gilusepppe C,et al.History of L-carnitine:Implications for renal disease[J].J Ren Nutr,2003,13(1):2-14
[4]Giafranco G,Roberta S,Gianni B.Carnitine metabolism in uremia[J].Am J Kidney Dis,2001,38(4):63-67
[5]Ramsay R.The carnitine acyltransferases:modulators of acyl- CoA-dependent reactions[J].Biochem Soci Tran,2000,28(2):182-186
[6]Angsten G,Cederblad G,Meurling S.Reference ranges for muscle carnitine concentration in children[J].Ann Clin Biochem,2003,,40(4):404-410
[7]林锋.左卡尼汀在全肠外营养中的应用[J].中华胃肠外科杂志,2003,3(1):42-44
[8]Angelini C,Vergani L,Martinuzzi A.Clinical and biochemical aspects of carnitine deficiency and insufficiency:transport defects and inborn errors of oxidation[J].Crit Rev Clin Lab Sci 1992;29(3-4):217-42
[9]Marzo A,Martelli EA,Mancinelli A,et al.Protein binding of L-carnitine family components.Participants Papers(Special Issue No Ⅲ).Eur J Drug Metab Pharmacokinet 1991,364-8
[10]Hurot J,Cucherat M,Haugh M,et al.Effects of L-carnitine supplementation in maintenance hemodialysis patients:A system-atic review[J].J Am Soc Nephrol,2002,13(3):708-714
[11]罗家琳,马培龙,张洪波.左卡尼汀治疗肾性贫血临床观察[J].中国血液净化,2003,2(10):565-566
[12]Lango R,Smolenski R,Narkiewicz M,et al.Influence of L-carnitine and its derivatives on myocardial metabolism and function in ischemic heart disease and during cardiopulmonary bypass[J].Cardiovasc Res,2001,51(1):21-29
[13]Zaugg C,M Spaniol,P Kaufmann,et al.Myocardial function and energymetabolism in carnitine deficient rats CMLS[J].Cell Mol Life Sci,2003,60(4):767-775
[14]Nemoto S,Aoki M,Dehua C,et al.Effects of carnitine on cardiac function after cardioplegic ischemia in neonatal rabbit hearts.Ann Thorac Surg,2001,71(1):254-259
[15]涂向阳,魏世超等.贝康亭治疗62例有机磷中毒心肌损害临床观察[J].福建医学杂志,2002,24(4):156
[16]Diaz M,Lopez F,Hernandez F,et al.L-Carnitine effects on chemical composition of plasma lipoproteins of rabbits fed with normal and high cholesterol diets[J].Lipids,2000,35(6):627-632
[17]Eskandari G,Kandemir O,Polat G,et al.Serum L-carnitine levels and lipoprotein compositions in chronic viral hepatitis Patients[J].Clin biochem,2000,34(5):431
[18]Malaguarnera M,Pistone G,Astuto M,et al.L-carnitine in the treatment of mild or moderate hepatic encephalopathy[J].Dig Dis,2000,21,(3):271
[19]杨金龙,夏子禹,游龙英,等.复方左卡尼汀治疗慢性病毒性肝炎[J].中国新药与临床杂,200,20(2):125-126
[20]施健,刘芬,谢渭芬.左卡尼汀的临床应用[J].中国临床药学杂志,2005,14(2):128-130.
[21]林修,叶榕,王耀新.卡尼汀治疗急性脑梗死[J].中国新药与临床杂志,2001,20(2):121
[22]Montgomery S,Thal L,Amrein R,et al.Meta-analysis of double-blind randomized controlled clinical trials of acetyl-L-carnitine versus placebo in the treatment of mild cognitive impairment and mild Alzheimer's disease[J].Int Clin Psychopharmacol,2003,18(2):61-71
[23]Benvenga S,Ruggeri R,Russo A,et al.Usefulness of L-camitine,a naturally accurally peripheral antagonist of thyroid hormone action in iatrogenic hyperthyroidism:a randomized,double-blind,placebo controlled clinical trial[J].J Clin Endocrinol Metab,2001,86(8):3579-3594.
[24]王咏梅,殷仁富,杜荣增,等.左旋卡尼汀对糖尿病伴高血压患者血浆肉碱浓度及血糖的影响[J].第二军医大学学报,2003,24(4):425.
[25]Benvenga S,Lapa D,Canavo S,et al.Successive thyroid storms treated with L-carnitine and low doses of methimazole[J].Am J Med,2003,115(5):417.
[26]Malone J,Schocken D,Morrison A,et al.Diabetic cardiomyopa2 thy and camitine deficiency[J].J Diabetes Complications,1999,13(2):86-89
[27]Dahlstrom K,Ament M,Moukarzel A,.et al.Low blood and plasma carnitine levels in children receiving long-term parenteral nutrition[J].J Pediatr Gastroenterol Nutr,1990,11(3):375-379
[28]Tibboel D,De Lemarre F,Przyrembel H.et al.Carnitine deficiency in surgical neonates receiving total parenteral nutrition[J].J Pediatr Surg,1990,25:418-421
[29]Center S,Harte J,Watrous D,et al.The clinical and metabolic effects of rapid weight loss in obese pet cats and the influence of supplemental oral L-carnitine[J].J Vet InternMed,2000,14(6):598-608
[30]Villani R,Gannon J,Self M,et al.L-Carnitine supplementation combined with aerobic training does not promote weight loss in moderately obese women[J].Int Sport Nutr Exerc Metab,2000,10(2 ):199-207
[31]Agarwal A,Said T.Carnitines and male infertility[J].Reprod Biomed Online,2004,8(4):376-384
[32]谷荣华等.高效液相色谱法测定不育男子精浆左卡尼汀及其临床意义[J].中国男科学杂志,2005,19(1):49-52
[33]De Simone C,Moretti S,Marcellini S,et al.L-Carnitine a modulator of immunometabolic homeostasis in subjects infected with the human immunodeficiency virus.In:De Simone C,Famularo G,editors.Carnitine today.Austin:Landes Bioscience,1997:215-31
[34]Murakami K,Sugimoto T,Woo M,et al.Effect of L-carnitine supplementation on acute valproate intoxication.Epilepsia 1996,37(7):687-9
[35]Bohan TP,Helton E,McDonald I,et al.Effect of L-carnitine treatment for valproate-induced hepatotoxicity.Neurology 2001,56(2):1405-8
[36]Kelly GS.L-Carnitine:therapeutic applications of a conditionally-essential amino acid.Altern Med Rev 1998,3(5):345-60
[37]Harper P,Elwin CE,Cederblad G.Pharmacokinetics of bolus intravenous and oral doses of L-carnitine in healthy subjects.Eur J Clin Pharmacol.1988;35(1):69-75
[38]Segre G,Bianchi E,Corsi M,et al.Plasma and urine pharmacokinetics of free and of short-chain carnitine after administration of carnitine in man.Arzneimittelforschung.1988,38(12):1830-4
[39]Baker H,Frank O,DeAngelis B,et al.Absorption and excretion of L-carnitine during single or multiple dosings in humans,Int J Vitam Nutr Res.1993;63(1):22-6.
[40]Sahajwalla CG,Helton ED,Purich ED,et al.Multiple-dose pharmacokinetics and bioequivalence of L-carnitine 330mg tablet versus 1 g chewable tablet versus enteral solution in healthy adult male volunteers.J Pharm Sci 1995;84(5):627-33.
[41]徐先彬,刘蕾,李可欣,等,HPLC法测定喷昔洛韦在健康人血浆浓度及其药代动力学研究[J].中国临床药理学杂志,2007,(23)2:147-150.
[42]Xia LJ,Folkers K.Improved methodology to assay carnitine and levels of free and total carnitine in human plasma.Biochern Biophys Res Commun 1991,176(3):1617-23
[43]Harper P,Elwin CE,Cederblad G.Pharmacokinetics of bolus intravenous and oral doses of L-carnitine in healthy subjects.Eur J Clin Pharmacol 1988,35:69-75
[44]Pearson D J,Tubbs PK.A sensitive enzymic assay for carnitine.Biochem J 1964,91(1):2C-4C
[45]Wieland OH,Deufel T,Paetzke-Brunner I.Free and esterified carnitine -colorimetric method.In:Bergmeyer H,editor.Methods of enzymatic analysis.Weinheim:Verlag Chemie,1985:481-8
[46]Mamoru Takahashi et al.carnitine determination by an enzymatic cycling method with carnitine dehydrogenase.Clin.Chem,1994,40(5):817-821
[47]刘惠兰,张晓洁,曹峰.血液透析患者静脉应用左旋肉碱(可益能)的药代动力学研究[J].中国血液净化,2003,2(6):298-310.
[48]MEI Chang-lin,XU Hong-shi,GU Shu-hua,et al.The determination of free carnitine and its clinical significance in hemodialysis patients.Chin J Med Lab Sci,1998,21(6):355-357.
[49]Rossle C,Kohse KP,Franz HE,et al.An improved method for the determination of free and esterfied carnitine.Clin Chem Acta,1985,149:263.
[50]Fuller RK,Hoppel CL.Elevated plasma carnitine in hepatic cirrhosis Hepatology,1983,3(4):554-556.
[51]De Sousa C,English NR,Stacey TE,et al.Measurement of L-carnitine and acylcarnitine in body fluids and tissues in children and in adults.Clin Chim Acta 1990;187:317-28
[52]Mamoru Takahashi,Shigeru Ueda,Hideo Misaki,et a/.Carnitine determination by an enzymatic cycling method with carnitine dehydrogenase.Clin.Cheat,1994;40(5):817-821
[53]Minkler PE,Ingalls ST,Hoppel.High-performance liquid chromatography separation of acylcarnitines following derivatization with 4'-bromophenacy trifluoromethylsulfonate.Anal Biochem,1990,185:29-32.
[54]Ke Li,Wei Li,Yufeng Huang.Determination of free L-carnitine in human seminal plasma by high performance liquid chromatography with pre-column ultraviolet derivatization and its clinical application in male infertility.Clinica Chirnica Acta 378(2007) 159-163
[55]Minkler PE,Hoppel CL.Quantification of free carnitine individual short-and medium-chain acylcarnitines and total carnitine in plasma by high-performance liquid chromatography.Anal Biochem 1993;212(2):510-8
[56]Minkler PE,Brass EP,Hiatt WR,et al.Quantification of carnitine,acetylcarnitine and total carnitine in tissues by high-performance liquid chromatography:the effect of exercise on carnitine homeostasis in man.Anal Biochem 1995;231:315-22
[57]Bhuiyan AK,Jackson S,Turnbull DM,et al.The measurement of carnitine and acyl-carnitine:application to the investigation of patients with suspected inherited disorders of mitochondrial fatty acid oxidation.Clin Chim Acta 1992;207(3):185-204
[58]Kamimori H,Hamashima Y,Konishi M.Determination of carnitine and saturated-acyl group carnitines in human urine by high-performance liquid chromatography with fluorescence detection.Anal Biochem 1994;218(2):417-27
[59]冯一,张顺国等.HPLC法测定血洁肉碱的研究[J].营养学报,2006,28(2):177-179
[60]丁峰,朱秋毓等.高效液相色谱法测定血浆游离肉碱.药物分析杂志,2005,25(10):1195-1197
[61]邵秀芬.严琳等.离子对RP-HPLC法测定左卡尼汀片剂的含量.药学进展,2004,28(3):131-134
[62]单林,宋国华等.反相高效液相色谱法测定肉碱.中国公共卫生.2001,17(5):457-458
[63]赵榕,孙开奇.离子对反相高效液相色谱法测定保健食品中肉碱.中国食品卫生.2002,14(4):25-26
[64]Lowes S,Rose ME,Mills GA.Identification of urinary acyl-carnitines using gas chromatography-mass spectrometry:preliminary clinical applications.J Chromatogr 1992;577(2):205-14
[65]Huang ZH,Gage DA,Bieber LL,et al.Analysis of acyl-carnitines as their N-demethylated ester derivatives by gas chroma-tography-chemical ionization mass spectrometry.Anal Biochem 1991;199(1):98-105
[66]Millington DS,Roe CR,Maltby DA.Application of high resolution fast atom bombardment and constant B/E ration linked scanning to the identification and analysis of acylcarnitines in metabolic disease.Biomed Mass Spectrom 1984;11(5):236-41
[67]Yergey AL,Liberato D J,Millington DS.Thermospray liquid chromatography/mass spectrometry for the analysis of L-carnitine and its short-chain acyl derivatives.Anal Biochem 1984;139(2):278-83
[68]Norwood DL,Kodo N,Millington DS.Application of continuous-flow liquid chromatography/fast-atom bombardment mass spectrometry to the analysis of diagnostic acylcarnitines in human urine.Rapid Commun Mass Spectrom 1988;2(12):269-72
[69]Gaskell SJ,Guenat C,Millington DS.Differentation of isomeric acylcarnitines using tandem mass spectrometry.Anal Chem 1986;58(13):2801-5
[70]Johnson AW,Mills K,Clayton PT.The use of automated electrospray ionization tandem MS for the diagnosis of inborn errors of metabolism from dried blood spots.Biochem Soc Trans 1996;24(3):932-8
[71]Vreken P,Van Lint AE,Bootsma AH,et al.Quantitative plasma acylcarnitine analysis using electrospray tandem mass spectrometry for the diagnosis of organic acidaemias and fatty acid oxidation defects.J Inherit Metab Dis 1999;22(3):302-6
[72]Chace DH,DiPerna JC,Mitchell BL,et al.Electrospray tandem mass spectrometry for analysis of acylcarnitines in dried post-mortem blood specimens collected at autopsy from infants with unexplained cause of death.Clin Chem 2001;47(7):1166-82
[73]Wiley V,Carpenter K,Wilcken B.Newborn screening with tandem mass spectrometry:12months' experience in NSW Australia.Acta Paediatr Suppl 1999;88(432):48-51
[74]Naylor EW,Chace DH.Automated tandem mass spectrometry for mass newborn screening for disorders in fatty acid,organic acid and amino acid metabolism.J Child Neurol 1999,14(1):S4-8
[75]Minkler PE,Ingalls ST,Hoppel.High-performance liquid chromatography separation of acylcarnitines following derivatization with 4'-bromophenacy trifluoromethylsulfonate,Anal Biochem,1990,185:29-32
[76]Lever M,Bason L,Leave C,et al.Same-day batch measurement of glycine betaine,carnitine and other betaines in biological material.Anal Biochem 1992,205:14
[77]丁峰,朱秋毓,顾勇,等高效液相色谱法测定血浆游离肉碱[J].药物分析杂志,2005,25(10):1195-1197
[78]赵亚明,李任,王得新,等.高效液相色谱法检测血浆左旋肉碱方法的建立[J].中国临床神经科学,2006,14(5):528-532.
[79]Evans AM,Faul R,Fornasini G,et al.Pharmacokinetics of L-carnitine in patients with end-stage renal disease undergoing long-term hemodialysis.Clin Pharmacol Ther 2000;68(3):238-49.
[80]Longo A,Bruno G,Curti S,et al.Determination of L-carnitine acetyl-L-carnitine and propionyl-L-carnitine in human plasma by high-performance liquid chromatography after pre-column derivitization with l-aminoanthracene.J Chromatogr B Bi.omed Appl 1996;686(2):129-39.
[81]Segre G,Bianchi E,Corsi M,et al.Plasma and urine pharmacokinetics of free and of short-chain caruitine after administration of carnitine in man.Arzneimittelforschung.1988 Dec;38(12):1830-4.
[82]Laurence V,Michael D,Jurg S,et al.Effect of L-carnitine on the kinetics of carnitine,acylcarnitines and butyrobetaine in long-term haemodialysis[J].Nephrol Dial Transplant,2006,21:450-458.
[83]Lombard KA,Olson AL,Nelson SE,et al.Carnitine status of lactoovovegetarians and strict vegetarian adults and children.Am J C1in Nutr 1989;50(2):301-6
[84]Engel AG,Rebouche CJ,Wilson DM,et al.Primary systemic carnitine deficiency:Ⅱ.renal handling of carnitine.Neurology 1981;31:819-25
[85]Bernardini I,Rizzo WB,Dalakas M,et al.Plasma and muscle free carnitine deficiency due to renal Fanconi syndrome.J Clin Invest 1985;75:1124-30
[86]Bellinghieri G,Savica V,Mallamace A,et al.Correlation between increased serum and tissue L-carnitine levels and improved muscle symptoms in hemodialyzed patients.Am J Clin Nutr 1983;38:523-31
[87]Ding Feng,Gu Yong,Lin Shantan,et al.The multicentre trabant study of curing carntine deficiency by giving levocarnitine[J].Shanghai medical science,2003,26(11):785-788.
[88]R Riva,F Albani,G Gobbi,et al.Carnitine disposition before and during valproate therapy in patients with epilepsy.Epilepsia,1993;34(1):184-7
[89]Angelo Mancinelli S.D'Iddio R.Bisonni F,et,al.Urinary excretion of L-carnitine and its short-chain acetyl-L-carnitine in patients undergoing carboplatin treatment.Cancer Chemother Pharmacol(2007) 60:19-26
[90]E De Palo,R Gatti,N Sicolo,et al.Plasma and urine free L-carnitine in human diabetes mellitus.Acta Diabetol Lat.1981:18(1):91-5.
[91]旷劲松,王福莉,李彦华,等.白碧玲肥胖症患者餐后利空腹血浆游离肉碱水平的检测及其意义[J]中国实用内科杂志,2004(24)2:97
[92]蔺小红,焦莉莉,徐国宾等.肝病患者血清肉碱水平的临床研究[J]中华肝脏病杂志,2006(14)5:367-369
[93]谷朵华,李铮,刘勇等.高效液相色谱法测定不育男子精浆左卡尼汀及其临床意义[J]中国男科学杂志,2005(19)1:48-49
[94]王福莉,刘国良.糖尿病伴冠心病患者血浆游离肉碱水平的相关性研究[J].中国误诊学杂志.2006,6(19):3687-3688
[95]赵亚明,王得新,吴丽娟等.脂肪累积性肌肉病患者血浆左旋肉碱含量测定的意义[J].中华神 经科杂志,2002(35):214-216
[96]赵亚明,刘古东,王得新.左旋肉碱治疗慢性疲劳综合征的研究[J].临床和实验医学杂志,2004,(3)3:133-135
[97]Takiyama N,Matsumoto K.Age-and sex-related differences of serum carnitine in a Japanese population.J Am Coll Nutr,1998,17:71-74
[98]RE Stevens,R Roy,KV Phelps.Evaluation of single- and multiple-dose pharmacokinetics of synthetic conjugated estrogens,A(Cenestin) tablets:a slow-release estrogen replacement product.J.Clin.Pharmacol.2002,42:332-341
[99]Yasuhito Fujisaka,Tomohide Tamura,Yuichiro Ohe,et al.Pharmacokinetics and Pharmacodynamics of Weekly Epoetin Beta in Lung Cancer Patients.Jpn J Clin Oncol 2006;36(8)477-482
[100]Wei Lu,Ph D,TGK Mant,et al.Pharmacokinetics of Recombinant Transgenic Antithrombin in Volunteers.Anesth Analg 2000;90:531-4
[101]John C,Roberts,Brent M,et al.Pharmacodynamic and Pharmacokinetic Studies of Agmatine after Spinal Administration in the Mouse.JPET,2005,314:1226-1233
[102]MATHIAS L,CLAUDE L,ALAIN B,et al.Bioavailability and Pharmacokinetics of Dehydroepiandrosterone in the Cynomolgus Monkey.J Clin Endocrinol Metab,2003,88(9):4293-4302
[103]GM Meno-Tetang,RA Blum,KE Schwartz,et al.Effects of oral prasterone (dehydroepiandrosterone) on single-dose pharmacokinetics of oral prednisone and cortisol suppression in normal women.J.Clin.Pharmacol.2001;41;1195-1205
[104]Robert H,Mathias L,Marianne SW,et al.Intranasal Loteprednol Etabonate in Healthy Male Subjects:Pharmacokinetics and Effects on Endogenous Cortisol.J.Clin.Pharmacol.2004;44;510-519
[105]James P.Thomas,Rhoda Z,et al.Phase I Pharmacokinetic and Pharmacodynamic Study of Recombinant Human Endostatin in Patients With Advanced Solid Tumors.Journal of Clinical Oncology,2003,21(2):223-231
[106]Amy E.Lovejoy,Tom C.Reynolds,Jennifer E,et al.Safety and pharmacokinetics of recombinant factor ⅩⅢ-A2 administration in patients with congenital factor ⅩⅢ deficiency.BLOOD,2006,108(1):57-62
[107]Gudjonsson H,Li B,Shug AL,et al.In vivo studies of intestinal carnitine absorption in rats.Gastroenterology 1985;88(6):1880-7.
[108]Rebouche CJ.Quantitative estimation of absorption and degradation of a carnitine supplement by human adults.Metabolism 1991;40(12):1305-10.
[1]J Kerner,C Hoppel.Generic disorders of carnitinemetabolism and their nutritional management [J].Annu Rev Nutr,1998,18:179-206.
[2]Reda E,Iddio D,Nicolai R,et al.The carnitine system and body composition[J].Acta Diabetol,2003,40(11):106-113.
[3]Mario M,Guido B,Gilusepppe C,et al.History of L-carnitine:Implications for renal disease[J].J Ren Nutr,2003,13(1):2-14.
[4]Giafranco G,Roberta S,Gianni B.Carnitine metabolism in uremia[J].Am J Kidney Dis,2001,38(4):63-67.
[5]Ramsay R.The carnitine acyltransferases:modulators of acyl-CoA-dependent reactions [J].Biochem SociTran,2000,28(2):182-186.
[6]Bahl JJ,Bressler R.The pharmacology of carnitine.Annu Rev Pharmacol Toxicol 1987;27:257-77
[7]Bremer J.The role of carnitine in cell metabolism.In:De Simone C,Famularo G,editors.Carnitine today.Austin:Landes Bioscience,1997:1-37
[8]Carter AL,Abney TO,Lapp DF.Biosynthesis and metabolism of carnitine.J Child Neurol 1995;10 Suppl.2:3-7
[9]Peluso G,Barbarisi A,Savica V,et al.Carnitine:an osmolyte that plays a metabolic role.J Cell Biochem 2000;80:1-10
[10]Angsten G,Cederblad G,Meurling S.Reference ranges for muscle carnitine concentration in children[J].Ann Clin Biochem,2003,,40(4):404-410.
[11]林锋.左卡尼汀在全肠外营养中的应用[J].中华胃肠外科杂志,2003,3(1):42-44.
[12]Marzo A,Martelli EA,Mancinelli A,et al.Protein binding of L-carnitine family components.Participants Papers(Special Issue No Ⅲ).Eur J Drug Metab Pharmacokinet 1991,364-8
[13]Hurot J,Cucherat M,Haugh M,et al.Effects of L-carnitine supplementation in maintenance hemodialysis patients:A system-atic review[J].J Am Soc Nephrol,2002,13(3):708-714.
[14]罗家琳,马培龙,张洪波.左卡尼汀治疗肾性贫血临床观察[J].中国血液净化,2003,2(10):565-566.
[15]Lango R,Smolenski R,Narkiewicz M,et al.Influence of L-carnitine and its derivatives on myocardial metabolism and function in ischemic heart disease and during cardiopulmonary bypass[J].Cardiovasc Res,2001,51(1):21-29.
[16]Zaugg C,M Spaniol,P Kaufmann,et al.Myocardial function and energymetabolism in carnitine deficient rats CMLS[J].CellMol Life Sci,2003,60(4):767-775.
[17]Nemoto S,Aoki M,Dehua C,et al.Effects of carnitine on cardiac function after cardioplegic ischemia in neonatal rabbit hearts.Ann Thorac Surg,2001,71(1):254-259.
[18]涂向际,魏世超等.贝康亭治疗62例有机磷中毒心肌损害临床观察[J].福建医学学杂志,2002,24(4):156.
[19]Diaz M,Lopez F,Hernandez F,et al.L-carnitine effects on chemical composition of plasma lipoproteins of rabbits fed with normal and high cholesterol diets[J].Lipids,2000,35(6):627-632.
[20]Eskandari G,Kandemir O,Polar G,et al.Serum L-carnitine levels and lipoprotein compositions in chronic viral hepatitis Patients[J].Clinbiochem,2000,34(5):431.
[21]Malaguarnera M,Pistone G,Astuto M,et al.L-carnitine in the treatment of mild or moderate hepatic encephalopathy[J].Dig Dis,2000,21,(3):271.
[22]杨金龙,夏子禹,游龙英,等.复方左卡尼汀治疗慢性病毒性肝炎[J].中国新药与临床杂,200,20(2):125-126.
[23]施健,刘芬,谢渭芬.左卡尼汀的临床应用[J].中国临床药学杂志,2005,14(2):128-130.
[24]林修,叶榕,王耀新.卡尼汀治疗急性脑梗死[J].中国新药与临床杂志,2001,20(2):121.
[25]Montgomery S,Thai L,Amrein R,et al.Meta-analysis of double-blind randomized controlled clinical trials of acetyl-L-carnitine versus placebo in the treatment of mild cognitive impairment and mild Alzheimer's disease[J].Int Clin Psychopharmacol,2003,18(2):61-71.
[26]Benvenga S,Ruggeri R,Russo A,et al.Usefulness of L-carnitine,a naturally accurally peripheral antagonist of thyroid hormone action in iatrogenic hyperthyroidism:a randomized,double-blind,placebo controlled clinical trial[J].J Clin Endocrinol Metab,2001,86(8):3579-3594.
[27]王咏梅,殷仁富,杜荣增,等.左旋卡尼汀对糖尿病伴高血压患者血浆左卡尼汀浓度及血糖的影响[J].第二军医大学学报,2003,24(4):425.
[28]Benvenga S,Lapa D,Canavo S,et al.Successive thyroid storms treated with L-carnitine and low doses of methimazole[J].Am J Med,2003,115(5):417.
[29]Malone J,Schocken D,Morrison A,et al.Diabetic cardiomyopa2 thy and carnitine deficiency[J].J Diabetes Complications,1999,13(2):86.
[30]Dahlstrom K,Ament M,Moukarzel A,et al.Low blood and plasma carnitine levels in children receiving long-term parenteral nutrition[J].J Pediatr Gastroenterol Nutr,1990,11(3):375-379.
[31]Tibboel D,De Lemarre F,Przyrembel H.et al.carnitine deficiency in surgical neonates receiving total parenteral nutrition[J].J Pediatr Surg,1990,25:418-421.
[32]Center S,Harte J,Watrous D,et al.The clinical and metabolic effects of rapid weight loss in obese pet cats and the influence of supplemental oral L-carnitine[J].J Vet InternMed,2000,14(6):598-608.
[33]Villani R,Gannon J,Self M,et al.L-Carnitine supplementation combined with aerobic training does not promote weight loss in moderately obese women[J].Int Sport Nutr Exerc Metab,2000,10(2):199-207.
[34]Agarwal A,Said T.Carnitines and male infertility[J].Reprod Biomed Online,2004,8(4):376-384.
[35]谷荣华等.高效液相色谱法测定不育男子精浆左卡尼汀及其临床意义[J].中国男科学杂志,2005,19(1):49.
[36]De Simone C,Moretti S,Marcellini S,et al.L-Carnitine a modulator of immunometabolic homeostasis in subjects infected with the human immunodeficiency virus.In:De Simone C,Famularo G,editors.Carnitine today.Austin:Landes Bioscience,1997:215-31
[37]Murakami K,Sugimoto T,Woo M,et al.Effect of L-carnitine supplementation on acute valproate intoxication.Epilepsia 1996;37(7):687-9
[38]Bohan TP,Helton E,McDonald I,et al.Effect of L-carnitine treatment for valproate-induced hepatotoxicity.Neurology 2001;56(2 of 2):1405-8
[39]Kelly GS.L-Carnitine:therapeutic applications of a conditionally-essential amino acid.Altern Med Rev 1998;3(5):345-60
[40]Travassos L.R.C.O.Sales.Microbiological assay of carnitine.Anal.Biochem,1974,58:485-499
[41]Friedman,S.Determination of carnitine in biological mat.erials.Arch.Biochem.Biophys,1958,75:24-31
[42]Fritz IB,Schulz SK,Srere PA.Properties of partially purified carnitine acetyltransferase.J Biol Chem 1963;238:2509-17
[43]Marquis NB,Fritz IB.Enzymological determination of free carnitine concentrations in rat tissue.J Lipid Res 1964;5:184-7
[44]Deufel T.Determination of L-carnitine in biological fluids and tissues.J Clin Chem Clin Biochem 1990;28(5):307-11
[45]陈肖燕,谢鑫友等.全自动酶法测定血清总合利游离卡尼汀浓度及临床应用[J].中华检验医学杂志,2003,26(12):764-767)
[46]Xia LJ,Folkers K.Improved methodology to assay carnitine and levels of free and total carnitine in human plasma.Biochem Biophys Res Commun 1991;176(3):1617-23
[47]Harper P,Elwin CE,Cederblad G.Pharmacokinetics of bolus intravenous and oral doses of L-carnitine in healthy subjects.Eur J Clin Pharmacol 1988;35:69-75
[48]Pearson DJ,Tubbs PK.A sensitive enzymic assay for carnitine.Biochem J 1964;91(1):2C-4C
[49]Wieland OH,Deufel T,Paetzke-Brunner I.Free and esterified carnitine -colorimetric method.In:Bergmeyer H,editor.Methods of enzymatic analysis.Weinheim:Verlag Chemic,1985:481-8
[50]Schafer,J.and Reichmann,H.A spectrophotometric method for the determination of free and esterified carnitine.Clinica Chimica Acta,1989,182:87-94.
[51]Williamson J.R,Schulz H,Fong J.C.Short-chain and long-chain enoyl-CoA hydratases from pig heart muscle[J],Methods Enzymology,1969,13:505-509
[52]Maehara M,Kinoshita S,Watanabe K.A simple fluorometric method for the determination of serum free carnitine.Clin Chim Acta.1988;171:311-316
[53]Mamoru Takahashi,Shigeru Ueda,Hideo Misaki,et al.Carnitine determination by an enzymatic cycling method with carnitine dehydrogenase.Clin.Chem,1994;40(5):817-821
[54]Cederblad G,Lindstedt S.A method for the determination of carnitine in the picomole range.Clin Chim Acta 1972;37:235-43
[55]Christiansen RZ,Bremer J.Acetylation of tris(hydroxymethy-1)aminomethane(tris) and tris derivatives by carnitine acetyl-transferase.FEBS Lett 1978;86(1):99-102
[56]Pace JA,Wannemacher RW,Neufeld HA.Improved radio-chemical assay for carnitine and its derivatives in plasma and tissue extracts.Clin Chem 1978;24(1):32-5
[57]Fishlock RC,Bieber LL,Snoswell AM.Sources of error in determinations of carnitine and acylcarnitine in plasma.Clin Chem 1984;30(2):316-8
[58]De Sousa C,English NR,Stacey TE,et al.Measurement of L-carnitine and acylcarnitine in body fluids and tissues in children and in adults.Clin Chim Acta 1990;187:317-28
[59]Kerner J,Bieber LL.A radioisotopic-exchange method for quantitation of short-chain (acid-soluble) acylcarnitines.Anal Biochem 1983;134:459-66
[60]Schmidt-Sommerfeld E,Penn D,Duran M,et al.Detection of inborn errors of fatty acid oxidation from acylcarnitine analysis of plasma and blood spots with the radioisotopic exchange-high-performance liquid chromatographic method.J Pediatr 1993;122(5 pt 1):708-14
[61]Schmidt-Sommerfeld E,Zhang L,Bobrowski P J,et al.Quantitation of short- and medium-chain acylcarnitines in plasma by radioisotopic exchange/high-performance liquid chromatography.Anal Biochem 1995;231(1):27-33
[62]Naoshi Takeyama,Yuji Iwanaga,Ken-ichi Kato,et al.Measurement of free and esterified carnitine in tissue extracts by high-performance liquid chromatography[J].Anal.Biochem,1986,158:346- 354
[63]Nobuhiko Arakawa,Yoshito Otake,Keisuke Hagio,et al.L-Carnitine Decreases Glycatin of Lens Proteins:in vitro studies[J].J.Nutr.Sci,Vitaminol,1989,35:475-479
[64]Minkler PE,Ingals ST,Hoppel CL.High-performance liquid chromatographic separation of acylcarnitines following derivatization with 4,'-bromophenacyl trifluoromethanesulfonate.Anal Biochem 1990;185:29-35
[65]Minkler PE,Hoppel CL.Quantification of free carnitine individual short-and medium-chain acylcarnitines and total carnitine in plasma by high-performance liquid chromatography.Anal Biochem 1993;212(2):510-8
[66]Minkler PE,Brass EP,Hiatt WR,et al.Quantification of carnitine,acetylcarnitine and total carnitine in tissues by high-performance liquid chromatography:the effect of exercise on carnitine homeostasis in man.Anal Biochem 1995;231:315-22
[67]Bhuiyan AK,Jackson S,Turnbull DM,et al.The measurement of carnitine and acyl-carnitine:application to the investigation of patients with suspected inherited disorders of mitochondrial fatty acid oxidation.Clin Chim Acta 1992;207(3):185-204
[68]Kamimori H,Hamashima Y,Konishi M.Determination of carnitine and saturated-acyl group carnitines in human urine by high-performance liquid chromatography with fluorescence detection.Anal Biochem 1994;218(2):417-27
[69]Longo A,Bruno G,Curti S,et al.Determination of L-carnitine acetyl-L-carnitine and propionyl-L-carnitine in human plasma by high-performance liquid chromatography after pre-column derivitization with l-aminoanthracene.J Chromatogr B Bi.omed Appl 1996;686(2):129-39
[70]冯一,张顺国等.HPLC法测定血清肉碱的研究[J].营养学报,2006,28(2):177-179;57
[71]丁峰,朱秋毓等.高效液相色谱法测定血.浆游离肉碱[J].药物分析杂志,2005,25(10):1195-1197
[72]邵秀芬.严琳等.离子对RP-HPLC法测定左卡尼汀片剂的含量[J].药学进展,2004,28(3):131-134
[73]单林,宋国华等.反相高效液相色谱法测定肉碱[J].中国公共卫生.2001,17(5):457-458
[74]赵榕,孙开奇.离子对反相高效液相色谱法测定保健食品中肉碱[J].中国食品卫生.2002,14(4):25-26
[75]Lowes S,Rose ME,Mills GA.Identification of urinary acyl-carnitines using gas chromatography-mass spectrometry:preliminary clinical applications.J Chromatogr 1992;577(2):205-14
[76]Huang ZH,Gage DA,Bieber LL,et al.Analysis of acyl-carnitines as their N-demethylated ester derivatives by gas chroma-tography-chemical ionization mass spectrometry.Anal Bio-chem 1991;199(1):98-105
[77]Millington DS,Roe CR,Maltby DA.Application of high resolution fast atom bombardment and constant B/E ration linked scanning to the identification and analysis of acylcarnitines in metabolic disease.Biomed Mass Spectrom 1984;11(5):236-41
[78]Yergey AL,Liberato D J,Millington DS.Thermospray liquid chromatography/mass spectrometry for the analysis of L-carnitine and its short-chain acyl derivatives.Anal Biochem 1984;139(2):278-83
[79]Norwood DL,Kodo N,Millington DS.Application of continuous-flow liquid chromatography/fast-atom bombardment mass spectrometry to the analysis of diagnostic acylcarnitines in human urine.Rapid Commun Mass Spectrom 1988;2(12):269-72
[80]Gaskell S J,Guenat C,Millington DS.Differentation of isomeric acylcarnitines using tandem mass spectrometry.Anal Chem 1986:,58(13):2801-5
[81]Johnson AW,Mills K,Clayton PT.The use of automated electrospray ionization tandem MS for the diagnosis of inborn errors of metabolism from dried blood spots.Biochem Soc Trans 1996;24(3):932-8
[82]Vreken P,Van Lint AE,Bootsma AH,et al.Quantitative plasma acylcarnitine analysis using electrospray tandem mass spectrometry for the diagnosis of organic acidaemias and fatty acid oxidation defects.J Inherit Metab Dis 1999;22(3):302-6
[83]Chace DH,DiPerna JC,Mitchell BL,et al.Electrospray tandem mass spectrometry for analysis of acylcarnitines in dried post-mortem blood specimens collected at autopsy from infants with unexplained cause of death.Clin Chem 2001;47(7):1166-82
[84]Wiley V,Carpenter K,Wilcken B.Newborn screening with tandem mass spectrometry:12months' experience in NSW Australia.Acta Paediatr Suppl 1999;88(432):48-51
[85]Naylor EW,Chace DH.Automated tandem mass spectrometry for mass newborn screening for disorders in fatty acid,organic acid and amino acid metabolism.J Child Neurol 1999;14 Suppl.1:S4-8
[86]Vaz FM,Wanders RJA.Carnitine biosynthesis in mammals.Biochem J 2002;361:417-29
[87]Lombard KA,Olson AL,Nelson SE,et al.Carnitine status of lactoovovegetarians and strict vegetarian adults and children.Am J Clin Nutr 1989;50(2):301-6
[88]Rebouche CJ.Carnitine function and requirements during the life cycle.FASEB J 1992 Dec;6:3379-86
[89]Rebouche CJ.Metabolic fate of dietary carnitine in humans.In:Lee Carter A,editor.Current concepts in carnitine research.Boca Raton & Ann Arbor:CRC Press,1992:37-48
[90]Cederblad G.Effect of diet on plasma carnitine levels and urinary carnitine excretion in humans.Am J Clin Nutr 1987;45(4):725-9
[91] Wiley V, Carpenter K, Wilcken B. Newborn screening with tandem mass spectrometry: 12 months' experience in NSW Australia. Acta Paediatr Suppl 1999; 88 (432): 48-51
[92] Rebouche CJ, Seim H. Carnitine metabolism and its regulation in microorganisms and mammals.AnnuRevNutr 1998; 18:39-61
[93] Bieber LL. Carnitine. Annu Rev Biochem 1988; 57: 261-833
[94] Rebouche CJ, Chenard CA. Metabolic fate of dietary carnitine in human adults: identification and quantification of urinary and fecal metabolites. J Nutr 1991; 121 (4): 539-46
[95] Rebouche CJ, Lombard KA, Chenard CA. Renal adaptation to dietary carnitine in humans. Am J Clin Nutr 1993; 58: 660-5
[96] Mancinelli A, Longo A, Shanahan K, et al. Disposition of L-carnitine and acetyl-L-carnitine in the isolated perfused rat kidney. J Pharmacol Exp Ther 1995; 274 (3): 1122-8
[97] Marzo A, Martelli EA, Mancinelli A, et al. Protein binding of L-carnitine family components.Participants Papers (Special Issue No III). Eur J Drug Metab Pharmacokinet 1991, 364-8
[98] Frolich J, Seccombe DW, Hahn P, et al. Effect of fasting on free and esterified carnitine levels in human serum and urine: correlation with serum levels of free fatty acids and b-hydrox-ybutyrate.Metabolism 1978; 27 (5): 555-61
[99] Engel AG, Rebouche CJ, Wilson DM, et al. Primary systemic carnitine deficiency: II. renal handling of camitine. Neurology 1981; 31: 819-25
[100] Stanley CA, Berry GT, Bennett MJ, et al. Renal handling of carnitine in secondary carnitine deficiency disorders. Pediatr Res 1993; 34: 89-97
[101] Bernardini I, Rizzo WB, Dalakas M, et al. Plasma and muscle free carnitine deficiency due to renal Fanconi syndrome. J Clin Invest 1985; 75: 1124-30
[102] Ohashi R, Tamai I, Nezu J, et al. Molecular and physiological evidence for multifunctionality of camitine/organic cation transporter OCTN2. Mol Pharmacol 2001; 59 (2): 358-66
[103] Tamai I, Ohashi R, Nezu J, et al. Molecular and functional identification of sodium ion-dependent, high affinity human carnitine transporter OCTN2. J Biol Chem 1998; 273(32):20378-82
[104] Wagner CA, Lukewille U, Kaltenbach S, et al. Functional and pharmacological characterization of human Na+-carnitine cotransporter hOCTN2. Am J Physiol Renal Physiol 2000; 279:F584-91
[105] Wang Y, Ye J, Ganpathy V, et al. Mutations in the organic cation/ carnitine transporter OCTN2 in primary carnitine deficiency. Proc Natl Acad Sci U S A 1999; 96: 2356-60
[106] Wu X, Huang W, Prasad PD, et al. Functional characteristics and tissue distribution pattern of organic cation transporter 2(OCTN2), an organic cation/carnitine transporter. J Pharmacol Exp Ther 1999; 290: 1482-92;
[107] Nezu J, Tamai I, Oku A, et al. Primary systemic carnitine deficiency is caused by mutations in a gene encoding sodium ion-dependent carnitine transporter. Nat Genet 1999; 21 (1):91-4
[108] Tang NL, Ganpathy V, Wu X, et al. Mutations of OCTN2, an organic cation/carnitine transporter, lead to deficient cellular carnitine uptake in primary carnitine deficiency. Hum Mol Genet 1999; 8: 655-60
[109] Angelini C, Vergani L, Martinuzzi A. Clinical and biochemical aspects of carnitine deficiency and insufficiency: transport defects and inborn errors of -oxidation. Crit Rev Clin Lab Sci 1992; 29 (3-4): 217-42
[110] Pons R, De Vivo DC. Primary and secondary carnitine deficiency syndromes. J Child Neurol 1995;10 Suppl.2:2S8-24
[111] Angelini C, Vergani L, Martinuzzi A. Clinical and biochemical aspects of carnitine deficiency and insufficiency: transport defects and inborn errors of -oxidation. Crit Rev Clin Lab Sci 1992; 29 (3-4): 217-42
[112] Bertoli M, Battistella PA, Vergani L, et al. Carnitine deficiency induced during hemodialysis and hyperlipidemia: effect of replacement therapy. Am J Clin Nutr 1981; 34: 1496-500
[113] Moorthy AV, Rosenblum M, Rajaram R, et al. A comparison of plasma and muscle carnitine levels in patients on peritoneal or hemodialysis for chronic renal failure. Am J Nephrol 1983;3:205-8;
[114] Brooks DE. Carnitine in the male reproductive tract and its relation to the metabolism of the epididymis and spermatozoa.In: Frenkel R, McGarry J, editors. Carnitine biosynthesis metabolism and function. New York: Academic Press, 1980:219-35
[115] Brass EP. Pharmacokinetic considerations for the therapeutic use of carnitine in hemodialysis patients. Clin Ther 1995; 17(2): 176-85
[116] Bellinghieri G, Savica V, Mallamace A, et al. Correlation between increased serum and tissue L-carnitine levels and improved muscle symptoms in hemodialyzed patients. Am J Clin Nutr 1983; 38:523-31
[117]Wanner C, Horl WH. Carnitine abnormalities in patients with renal insufficiency:pathophysiological and therapeutical aspects. Nephron 1988; 50: 89-102
[118] Famularo G, Matricardi F, Nucera E, et al. Carnitine deficiency: primary and secondary syndromes. In: De Simone C, Famularo G, editors. Carnitine today. Austin: Landes Bioscience,1997:119-61
[119]Cooper MB, Forte CA, Jones DA. Carnitine and acetylcarnitine in red blood cells. Biochim Biophys Acta 1988; 959: 100-5
[120] Gudjonsson H, Li B, Shug AL, et al. In vivo studies of intestinal carnitine absorption in rats.Gastroenterology 1985; 88 (6): 1880-7
[121] Matsuda K, Yuasa H, Watanabe J. Physiological mechanism based analysis of dose-dependent gastrointestinal absorption of L-carnitine in rats. Biopharm Drug Dispos 1998; 19: 465-72
[122] Matsuda K, Yuasa H, Watanabe J. Fractional absorption of L-carnitine after oral administration in rats: evaluation of absorption site and dose dependency. Biol Pharm Bull 1998; 21 (7):752-5
[123] Gross CJ, Henderson LM, Savaiano DA. Uptake of L-carnitine,D-carnitine and acetyl-L-carnitine by isolate guinea-pig enter ocytes. Biochim Biophys Acta 1986; 886: 425-33
[124] Shaw RD, Li B, Hamilton JW, et al. Carnitine transport in rat small intestine. Am J Physiol 1983;245:G376-81
[125] Hamilton JW, Li B, Shug AL, et al. Carnitine transport in human intestinal biopsy specimens:demonstration of an active transport system. Gastroenterology 1986; 91 (1): 10-6
[126] McCloud E, Ma TY, Grant KE, et al. Uptake of L-carnitine by human intestinal epithelial cell line, Caco 2. Gastroenterology 1996; 111 (6): 1534-40
[127] Gross CJ, Henderson LM. Absorption of D- and L-carnitine by the intestine and kidney tubule in the rat. Biochim Biophys Acta 1984; 772: 209-19
[128] Sahajwalla CG, Helton ED, Punch ED, et al. Multiple-dose pharmacokinetics and bioequivalence of L-carnitine 330mg tablet versus 1g chewable tablet versus enteral solution in healthy adult male volunteers. J Pharm Sci 1995; 84 (5):627-33
[129] Segre G, Bianchi E, Corsi M, et al. Plasma and urine pharmacokinetics of free and of short-chain carnitine after administration of carnitine in man. Arzneimittel Forschung 1988; 38 (II)(12):1830-4
[130] Harper P, Elwin CE, Cederblad G. Pharmacokinetics of bolus intravenous and oral doses of L-carnitine in healthy subjects. Eur J Clin Pharmacol 1988; 35: 69-75
[131] Rizza V, Lorefice R, Rizza N, et al. Pharmacokinetics of L-carnitine in human subjects. In:Ferrari R, Dimauro S, Sher wood G, editors. L-Carnitine and its role in medicine: from function to therapy. New York: Academic Press, 1992: 63-77
[132] Borum PR. Plasma carnitine compartment and red blood cell carnitine compartment of healthy adults.Am J Clin Nutr,1987,46:437-441
[133] Sahajwalla CG, Helton ED, Purich ED, et al. Comparison of L-carnitine pharmacokinetics with and without baseline correction following administration of single 20mg/kg intravenous dose. J Pharm Sci 1995;84(5):634-9
[134] Rebouche CJ, Engel AG. Kinetic compartmental analysis of carnitine metabolism in the human carnitine deficiency syndromes. J Clin Invest 1984 Mar; 73 (3): 857-67
[135] Dippenaar N, Clauss RP, Feinendegen LE. Effect of carnitine and essential fatty acid supplementation on the uptake of 11C-carnitine in muscle of a myopathic carnitine-deficient patient using positron emission scintigraphy. Prostaglandins Leukot Essent Fatty Acids 1998; 58(3): 201-4
[136] Brooks DE, McIntosh JE. Turnover of carnitine by rat tissues. Biochem J 1975; 148 (3): 439-45
[137] Cederblad G, Lindstedt S. Metabolism of labeled carnitine in the rat. Arch Biochem Biophys 1976; 175: 173-80;
[138] Rebouche C, Engel A. Kinetic compartmental analysis of carnitine metabolism in the dog. Arch Biochem Biophys 1983; 220:60-70
[139] Khairallah EA, Wolf G. Carnitine decarboxylase: the conversion of carnitine to-methylcholine. J Biol Chem 1967; 242(1): 32-9
[140] Rebouche CJ. Quantitative estimation of absorption and degradation of a carnitine supplement by human adults. Metabolism 1991; 40 (12): 1305-10
[141] Zhang AQ, Mitchell SC, Smith RL. Discontinuous distribution of n-oxidation of dietary-derived trimethylamine in a British population. Xenobiotica 1996; 26 (9): 957-61
[142] Zhang AQ, Mitchell SC, Smith RL. Dietary precursors of trimethylamine in man: a pilot study.Food Chem Toxicol 1999; 37: 515-20
[143] Ayesh R, Mitchell SC, Zhang A, et al. The fish odour syndrome: biochemical familial and clinical aspects. BMJ 1993;307 (6905): 655-7
[144] Humbert JR, Hammond KB, Hathaway WE, et al. Trimethy-laminuria: the fish-odour syndrome.Lancet 1970; II(7676):770-l
[145] Mitchell SC. The fish-odour syndrome. Perspect Biol Med 1996; 39 (4): 514-26
[146] Mitchell SC, Zhang AQ, Smith RL. Fish-odour syndrome and impaired n-oxidation. Biochem Soc Trans 1996; 24(1): 965
[147] Al-Waiz M, Ayesh R, Mitchell SC, et al. Disclosure of the metabolic retroversion of trimethylamine N-oxide in humans:a pharmacogenetic approach. Clin Pharmacol Ther 1987;42(6): 608-12
[148] Zeisel S, Da Costa K, Ox J. Endogenous formation of dimethylamine.Biochem J 1975; 232 (2):403-8
[149] Mitchell SC, Zhang A, Smith RL, et al. Trimethylamine noxide as a probable source of urinary dimethylamine in man; a statistical approach. Biochem Soc Trans 1998; 26 (2): S182
[150] Zhang AQ, Mitchell SC, Ayesh R, et al. Dimethylamine formation in man. Biochem Pharmacol 1993; 45 (11): 2185-8
[151] Sahajwalla CG, Helton ED, Purich ED, et al. Multiple-dose pharmacokinetics and bioequivalence of L-carnitine 330mg tablet versus 1g chewable tablet versus enteral solution in healthy adult male volunteers. J Pharm Sci 1995; 84 (5):627-33
[152] Hokland BM, Bremer J. Metabolism and excretion of carnitine and acylcarnitines in the perfused rat kidney. Biochim Biophys Acta 1986; 886 (2): 223-30
[153] Rebouche CJ, Engel AG. Carnitine metabolism and deficiency syndrome. Mayo Clin Proc 1983 Aug; 58: 533-40
[154] Pons R, Carrozzo R, Tein I, et al. Deficient muscle carnitine transport in primary carnitine deficiency. Pediatr Res 1997; 42:583-7
[155] Rebouche CJ, Paulson DJ. Carnitine metabolism and function in humans. Annu Rev Nutr 1986;6: 41-66
[156] Rose SJ, Stokes TC, Patel S, et al. Carnitine deficiency associated with long-term pivampicillin treatment: the effect of a replacement therapy regime. Postgrad Med J 1992; 68: 932-4
[157] Holme E, Jodal U, Linstedt S, et al. Effects of pivalic acid containing prodrugs on carnitine homeostasis and on response to fasting in children. Scand J Clin Lab Invest 1992; 52 (5):361-72
[158] Dalakas MC, Leon-Monzon ME, Bernardini I, et al. Zidovu-dine-induced mitochondrial myopathy is associated with muscle carnitine deficiency and lipid storage. Ann Neurol 1994; 35(4): 482-7
[159] Ross NS, Hoppel CL. Partial muscle carnitine palmitoyltrans-ferase-A deficiency. JAMA 1987;257(1): 62-5
[160] Ganapathy V, Huang W, Rajan DP, et al. Beta-lactam antibiotics as substrates for OCTN2, an organic cation/carnitine transporter. J Biol Chem 2000; 275 (3): 1699-707
[161] Ohtani Y, Nishiyama S, Matsuda I. Renal handling of free and acylcarnitine in secondary carnitine deficiency. Neurology 1984; 34 (7): 977-9
[162] Krahenbuhl S, Reichen J. Carnitine metabolism in patients with chronic liver disease. Hepatology 1996;25: 148-53
[163] Bartel LL, Hussey JL, Shrago E. Perturbation of serum carnitine levels in human adults by chronic renal disease and dialysis therapy. Am J Clin Nutr 1981 Jul; 34: 1314-20
[164] Rodriguez-Segade S, de la Pe~na CA, Paz M, et al. Carnitine concentrations in dialysed and undialysed patients with chronic renal insufficiency. Ann Clin Biochem 1986; 23: 671-5
[165] Ahmad S. Carnitine, kidney and renal dialysis: carnitine and the kidney. In: Ferrari R, Dimauro S, Sherwood G, editors. L-Carnitine and its role in medicine: from function to therapy. New York: Academic Press, 1992: 381-400
[166] Bohmer T, Bergrem H, Eiklid K. Carnitine deficiency induced during intermittent haemodialysis for renal failure. Lancet 1978; I (8056): 126-8
[167] Perm D, Schmidt-Sommerfeld E. Carnitine and carnitine esters in plasma and adipose tissue of chronic uremic patients under, going hemodialysis. Metabolism 1983; 32 (8): 806-9
[168] Vacha GM, Corsi M, Giorcelli G, et al. Serum and muscle L-carnitine levels in hemodialyzed patients during and after long-term L-carnitine treatment. Curr Ther Res 1985; 37 (3): 505-16
[169]. Jackson JM, Lee HA. L-Carnitine and acetyl-L-carnitine status during hemodialysis with acetate in humans: a kinetic analysis. Am J Clin Nutr 1996; 64: 922-7
[170]Guarnieri G,Toigo G,Crapesi L,et al.carnitine metabolism in chronic renal failure.Kidney Int Suppl 1987;32 Suppl.22:S116-27
[171]Sakurauchi Y,Matsumoto Y,Shinzato T,et al.Effects of L-carnitine supplementation on muscular symptoms in hemodi-alyzed patients.Am J Kidney Dis 1998;32(2):258-64
[172]Golper TA,Wolfson M,Ahmad S,et al.Multicenter trial of Lcarnitine in maintenance hemodialysis patients:I.carnitine concentrations and lipid effects.Kidney Int 1990;38:904-11
[173]Siami G,Clinton ME,Mrak R,et al.Evaluation of the effect of intravenous L-carnitine therapy on function structure and fatty acid metabolism of skeletal muscle in patients receiving chronic hemodialysis.Nephron 1991;57:306-13
[174]Savica V,Bellinghieri G,Di Stefano C,et al.Plasma and muscle carnitine levels in haemodialysis patients with morpho-logical-ultrastructural examination of muscle samples.Nephron 1983;35:232-6
[175]Debska-Slizien A,Kawecka A,Wojnarowski K,et al.Correlation between plasma carnitine muscle carnitine and glycogen levels in maintenance hemodialysis patients.Int J Artif Organs 2000;23(2):90-6;
[176]Evans AM,Faul R,Fornasini G,et al.Pharmacokinetics of L-carnitine in patients with end-stage renal disease undergoing long-term hemodialysis.Clin Pharmacol Ther 2000;68(3):238-49
[177]刘慧兰,张晓沾,等.血液透析患者静脉静脉应用左旋肉碱(可益能)的药代动力学研究.[J]中国血液挣化,2003,2(6):298-310
[178]Savica V,Bellinghieri G,Di Stefano C,et al.Plasma and muscle carnitine levels in haemodialysis patients with morpho-logical-ultrastructural examination of muscle samples.Nephron 1983;35:232-6
[2]Reda E,Iddio D,Nicolai R,et al.The carnitine system and body composition[J].Acta Diabetol,2003,40(1):106-113
[3]Mario M,Guido B,Gilusepppe C,et al.History of L-carnitine:Implications for renal disease[J].J Ren Nutr,2003,13(1):2-14
[4]Giafranco G,Roberta S,Gianni B.Carnitine metabolism in uremia[J].Am J Kidney Dis,2001,38(4):63-67
[5]Ramsay R.The carnitine acyltransferases:modulators of acyl- CoA-dependent reactions[J].Biochem Soci Tran,2000,28(2):182-186
[6]Angsten G,Cederblad G,Meurling S.Reference ranges for muscle carnitine concentration in children[J].Ann Clin Biochem,2003,,40(4):404-410
[7]林锋.左卡尼汀在全肠外营养中的应用[J].中华胃肠外科杂志,2003,3(1):42-44
[8]Angelini C,Vergani L,Martinuzzi A.Clinical and biochemical aspects of carnitine deficiency and insufficiency:transport defects and inborn errors of oxidation[J].Crit Rev Clin Lab Sci 1992;29(3-4):217-42
[9]Marzo A,Martelli EA,Mancinelli A,et al.Protein binding of L-carnitine family components.Participants Papers(Special Issue No Ⅲ).Eur J Drug Metab Pharmacokinet 1991,364-8
[10]Hurot J,Cucherat M,Haugh M,et al.Effects of L-carnitine supplementation in maintenance hemodialysis patients:A system-atic review[J].J Am Soc Nephrol,2002,13(3):708-714
[11]罗家琳,马培龙,张洪波.左卡尼汀治疗肾性贫血临床观察[J].中国血液净化,2003,2(10):565-566
[12]Lango R,Smolenski R,Narkiewicz M,et al.Influence of L-carnitine and its derivatives on myocardial metabolism and function in ischemic heart disease and during cardiopulmonary bypass[J].Cardiovasc Res,2001,51(1):21-29
[13]Zaugg C,M Spaniol,P Kaufmann,et al.Myocardial function and energymetabolism in carnitine deficient rats CMLS[J].Cell Mol Life Sci,2003,60(4):767-775
[14]Nemoto S,Aoki M,Dehua C,et al.Effects of carnitine on cardiac function after cardioplegic ischemia in neonatal rabbit hearts.Ann Thorac Surg,2001,71(1):254-259
[15]涂向阳,魏世超等.贝康亭治疗62例有机磷中毒心肌损害临床观察[J].福建医学杂志,2002,24(4):156
[16]Diaz M,Lopez F,Hernandez F,et al.L-Carnitine effects on chemical composition of plasma lipoproteins of rabbits fed with normal and high cholesterol diets[J].Lipids,2000,35(6):627-632
[17]Eskandari G,Kandemir O,Polat G,et al.Serum L-carnitine levels and lipoprotein compositions in chronic viral hepatitis Patients[J].Clin biochem,2000,34(5):431
[18]Malaguarnera M,Pistone G,Astuto M,et al.L-carnitine in the treatment of mild or moderate hepatic encephalopathy[J].Dig Dis,2000,21,(3):271
[19]杨金龙,夏子禹,游龙英,等.复方左卡尼汀治疗慢性病毒性肝炎[J].中国新药与临床杂,200,20(2):125-126
[20]施健,刘芬,谢渭芬.左卡尼汀的临床应用[J].中国临床药学杂志,2005,14(2):128-130.
[21]林修,叶榕,王耀新.卡尼汀治疗急性脑梗死[J].中国新药与临床杂志,2001,20(2):121
[22]Montgomery S,Thal L,Amrein R,et al.Meta-analysis of double-blind randomized controlled clinical trials of acetyl-L-carnitine versus placebo in the treatment of mild cognitive impairment and mild Alzheimer's disease[J].Int Clin Psychopharmacol,2003,18(2):61-71
[23]Benvenga S,Ruggeri R,Russo A,et al.Usefulness of L-camitine,a naturally accurally peripheral antagonist of thyroid hormone action in iatrogenic hyperthyroidism:a randomized,double-blind,placebo controlled clinical trial[J].J Clin Endocrinol Metab,2001,86(8):3579-3594.
[24]王咏梅,殷仁富,杜荣增,等.左旋卡尼汀对糖尿病伴高血压患者血浆肉碱浓度及血糖的影响[J].第二军医大学学报,2003,24(4):425.
[25]Benvenga S,Lapa D,Canavo S,et al.Successive thyroid storms treated with L-carnitine and low doses of methimazole[J].Am J Med,2003,115(5):417.
[26]Malone J,Schocken D,Morrison A,et al.Diabetic cardiomyopa2 thy and camitine deficiency[J].J Diabetes Complications,1999,13(2):86-89
[27]Dahlstrom K,Ament M,Moukarzel A,.et al.Low blood and plasma carnitine levels in children receiving long-term parenteral nutrition[J].J Pediatr Gastroenterol Nutr,1990,11(3):375-379
[28]Tibboel D,De Lemarre F,Przyrembel H.et al.Carnitine deficiency in surgical neonates receiving total parenteral nutrition[J].J Pediatr Surg,1990,25:418-421
[29]Center S,Harte J,Watrous D,et al.The clinical and metabolic effects of rapid weight loss in obese pet cats and the influence of supplemental oral L-carnitine[J].J Vet InternMed,2000,14(6):598-608
[30]Villani R,Gannon J,Self M,et al.L-Carnitine supplementation combined with aerobic training does not promote weight loss in moderately obese women[J].Int Sport Nutr Exerc Metab,2000,10(2 ):199-207
[31]Agarwal A,Said T.Carnitines and male infertility[J].Reprod Biomed Online,2004,8(4):376-384
[32]谷荣华等.高效液相色谱法测定不育男子精浆左卡尼汀及其临床意义[J].中国男科学杂志,2005,19(1):49-52
[33]De Simone C,Moretti S,Marcellini S,et al.L-Carnitine a modulator of immunometabolic homeostasis in subjects infected with the human immunodeficiency virus.In:De Simone C,Famularo G,editors.Carnitine today.Austin:Landes Bioscience,1997:215-31
[34]Murakami K,Sugimoto T,Woo M,et al.Effect of L-carnitine supplementation on acute valproate intoxication.Epilepsia 1996,37(7):687-9
[35]Bohan TP,Helton E,McDonald I,et al.Effect of L-carnitine treatment for valproate-induced hepatotoxicity.Neurology 2001,56(2):1405-8
[36]Kelly GS.L-Carnitine:therapeutic applications of a conditionally-essential amino acid.Altern Med Rev 1998,3(5):345-60
[37]Harper P,Elwin CE,Cederblad G.Pharmacokinetics of bolus intravenous and oral doses of L-carnitine in healthy subjects.Eur J Clin Pharmacol.1988;35(1):69-75
[38]Segre G,Bianchi E,Corsi M,et al.Plasma and urine pharmacokinetics of free and of short-chain carnitine after administration of carnitine in man.Arzneimittelforschung.1988,38(12):1830-4
[39]Baker H,Frank O,DeAngelis B,et al.Absorption and excretion of L-carnitine during single or multiple dosings in humans,Int J Vitam Nutr Res.1993;63(1):22-6.
[40]Sahajwalla CG,Helton ED,Purich ED,et al.Multiple-dose pharmacokinetics and bioequivalence of L-carnitine 330mg tablet versus 1 g chewable tablet versus enteral solution in healthy adult male volunteers.J Pharm Sci 1995;84(5):627-33.
[41]徐先彬,刘蕾,李可欣,等,HPLC法测定喷昔洛韦在健康人血浆浓度及其药代动力学研究[J].中国临床药理学杂志,2007,(23)2:147-150.
[42]Xia LJ,Folkers K.Improved methodology to assay carnitine and levels of free and total carnitine in human plasma.Biochern Biophys Res Commun 1991,176(3):1617-23
[43]Harper P,Elwin CE,Cederblad G.Pharmacokinetics of bolus intravenous and oral doses of L-carnitine in healthy subjects.Eur J Clin Pharmacol 1988,35:69-75
[44]Pearson D J,Tubbs PK.A sensitive enzymic assay for carnitine.Biochem J 1964,91(1):2C-4C
[45]Wieland OH,Deufel T,Paetzke-Brunner I.Free and esterified carnitine -colorimetric method.In:Bergmeyer H,editor.Methods of enzymatic analysis.Weinheim:Verlag Chemie,1985:481-8
[46]Mamoru Takahashi et al.carnitine determination by an enzymatic cycling method with carnitine dehydrogenase.Clin.Chem,1994,40(5):817-821
[47]刘惠兰,张晓洁,曹峰.血液透析患者静脉应用左旋肉碱(可益能)的药代动力学研究[J].中国血液净化,2003,2(6):298-310.
[48]MEI Chang-lin,XU Hong-shi,GU Shu-hua,et al.The determination of free carnitine and its clinical significance in hemodialysis patients.Chin J Med Lab Sci,1998,21(6):355-357.
[49]Rossle C,Kohse KP,Franz HE,et al.An improved method for the determination of free and esterfied carnitine.Clin Chem Acta,1985,149:263.
[50]Fuller RK,Hoppel CL.Elevated plasma carnitine in hepatic cirrhosis Hepatology,1983,3(4):554-556.
[51]De Sousa C,English NR,Stacey TE,et al.Measurement of L-carnitine and acylcarnitine in body fluids and tissues in children and in adults.Clin Chim Acta 1990;187:317-28
[52]Mamoru Takahashi,Shigeru Ueda,Hideo Misaki,et a/.Carnitine determination by an enzymatic cycling method with carnitine dehydrogenase.Clin.Cheat,1994;40(5):817-821
[53]Minkler PE,Ingalls ST,Hoppel.High-performance liquid chromatography separation of acylcarnitines following derivatization with 4'-bromophenacy trifluoromethylsulfonate.Anal Biochem,1990,185:29-32.
[54]Ke Li,Wei Li,Yufeng Huang.Determination of free L-carnitine in human seminal plasma by high performance liquid chromatography with pre-column ultraviolet derivatization and its clinical application in male infertility.Clinica Chirnica Acta 378(2007) 159-163
[55]Minkler PE,Hoppel CL.Quantification of free carnitine individual short-and medium-chain acylcarnitines and total carnitine in plasma by high-performance liquid chromatography.Anal Biochem 1993;212(2):510-8
[56]Minkler PE,Brass EP,Hiatt WR,et al.Quantification of carnitine,acetylcarnitine and total carnitine in tissues by high-performance liquid chromatography:the effect of exercise on carnitine homeostasis in man.Anal Biochem 1995;231:315-22
[57]Bhuiyan AK,Jackson S,Turnbull DM,et al.The measurement of carnitine and acyl-carnitine:application to the investigation of patients with suspected inherited disorders of mitochondrial fatty acid oxidation.Clin Chim Acta 1992;207(3):185-204
[58]Kamimori H,Hamashima Y,Konishi M.Determination of carnitine and saturated-acyl group carnitines in human urine by high-performance liquid chromatography with fluorescence detection.Anal Biochem 1994;218(2):417-27
[59]冯一,张顺国等.HPLC法测定血洁肉碱的研究[J].营养学报,2006,28(2):177-179
[60]丁峰,朱秋毓等.高效液相色谱法测定血浆游离肉碱.药物分析杂志,2005,25(10):1195-1197
[61]邵秀芬.严琳等.离子对RP-HPLC法测定左卡尼汀片剂的含量.药学进展,2004,28(3):131-134
[62]单林,宋国华等.反相高效液相色谱法测定肉碱.中国公共卫生.2001,17(5):457-458
[63]赵榕,孙开奇.离子对反相高效液相色谱法测定保健食品中肉碱.中国食品卫生.2002,14(4):25-26
[64]Lowes S,Rose ME,Mills GA.Identification of urinary acyl-carnitines using gas chromatography-mass spectrometry:preliminary clinical applications.J Chromatogr 1992;577(2):205-14
[65]Huang ZH,Gage DA,Bieber LL,et al.Analysis of acyl-carnitines as their N-demethylated ester derivatives by gas chroma-tography-chemical ionization mass spectrometry.Anal Biochem 1991;199(1):98-105
[66]Millington DS,Roe CR,Maltby DA.Application of high resolution fast atom bombardment and constant B/E ration linked scanning to the identification and analysis of acylcarnitines in metabolic disease.Biomed Mass Spectrom 1984;11(5):236-41
[67]Yergey AL,Liberato D J,Millington DS.Thermospray liquid chromatography/mass spectrometry for the analysis of L-carnitine and its short-chain acyl derivatives.Anal Biochem 1984;139(2):278-83
[68]Norwood DL,Kodo N,Millington DS.Application of continuous-flow liquid chromatography/fast-atom bombardment mass spectrometry to the analysis of diagnostic acylcarnitines in human urine.Rapid Commun Mass Spectrom 1988;2(12):269-72
[69]Gaskell SJ,Guenat C,Millington DS.Differentation of isomeric acylcarnitines using tandem mass spectrometry.Anal Chem 1986;58(13):2801-5
[70]Johnson AW,Mills K,Clayton PT.The use of automated electrospray ionization tandem MS for the diagnosis of inborn errors of metabolism from dried blood spots.Biochem Soc Trans 1996;24(3):932-8
[71]Vreken P,Van Lint AE,Bootsma AH,et al.Quantitative plasma acylcarnitine analysis using electrospray tandem mass spectrometry for the diagnosis of organic acidaemias and fatty acid oxidation defects.J Inherit Metab Dis 1999;22(3):302-6
[72]Chace DH,DiPerna JC,Mitchell BL,et al.Electrospray tandem mass spectrometry for analysis of acylcarnitines in dried post-mortem blood specimens collected at autopsy from infants with unexplained cause of death.Clin Chem 2001;47(7):1166-82
[73]Wiley V,Carpenter K,Wilcken B.Newborn screening with tandem mass spectrometry:12months' experience in NSW Australia.Acta Paediatr Suppl 1999;88(432):48-51
[74]Naylor EW,Chace DH.Automated tandem mass spectrometry for mass newborn screening for disorders in fatty acid,organic acid and amino acid metabolism.J Child Neurol 1999,14(1):S4-8
[75]Minkler PE,Ingalls ST,Hoppel.High-performance liquid chromatography separation of acylcarnitines following derivatization with 4'-bromophenacy trifluoromethylsulfonate,Anal Biochem,1990,185:29-32
[76]Lever M,Bason L,Leave C,et al.Same-day batch measurement of glycine betaine,carnitine and other betaines in biological material.Anal Biochem 1992,205:14
[77]丁峰,朱秋毓,顾勇,等高效液相色谱法测定血浆游离肉碱[J].药物分析杂志,2005,25(10):1195-1197
[78]赵亚明,李任,王得新,等.高效液相色谱法检测血浆左旋肉碱方法的建立[J].中国临床神经科学,2006,14(5):528-532.
[79]Evans AM,Faul R,Fornasini G,et al.Pharmacokinetics of L-carnitine in patients with end-stage renal disease undergoing long-term hemodialysis.Clin Pharmacol Ther 2000;68(3):238-49.
[80]Longo A,Bruno G,Curti S,et al.Determination of L-carnitine acetyl-L-carnitine and propionyl-L-carnitine in human plasma by high-performance liquid chromatography after pre-column derivitization with l-aminoanthracene.J Chromatogr B Bi.omed Appl 1996;686(2):129-39.
[81]Segre G,Bianchi E,Corsi M,et al.Plasma and urine pharmacokinetics of free and of short-chain caruitine after administration of carnitine in man.Arzneimittelforschung.1988 Dec;38(12):1830-4.
[82]Laurence V,Michael D,Jurg S,et al.Effect of L-carnitine on the kinetics of carnitine,acylcarnitines and butyrobetaine in long-term haemodialysis[J].Nephrol Dial Transplant,2006,21:450-458.
[83]Lombard KA,Olson AL,Nelson SE,et al.Carnitine status of lactoovovegetarians and strict vegetarian adults and children.Am J C1in Nutr 1989;50(2):301-6
[84]Engel AG,Rebouche CJ,Wilson DM,et al.Primary systemic carnitine deficiency:Ⅱ.renal handling of carnitine.Neurology 1981;31:819-25
[85]Bernardini I,Rizzo WB,Dalakas M,et al.Plasma and muscle free carnitine deficiency due to renal Fanconi syndrome.J Clin Invest 1985;75:1124-30
[86]Bellinghieri G,Savica V,Mallamace A,et al.Correlation between increased serum and tissue L-carnitine levels and improved muscle symptoms in hemodialyzed patients.Am J Clin Nutr 1983;38:523-31
[87]Ding Feng,Gu Yong,Lin Shantan,et al.The multicentre trabant study of curing carntine deficiency by giving levocarnitine[J].Shanghai medical science,2003,26(11):785-788.
[88]R Riva,F Albani,G Gobbi,et al.Carnitine disposition before and during valproate therapy in patients with epilepsy.Epilepsia,1993;34(1):184-7
[89]Angelo Mancinelli S.D'Iddio R.Bisonni F,et,al.Urinary excretion of L-carnitine and its short-chain acetyl-L-carnitine in patients undergoing carboplatin treatment.Cancer Chemother Pharmacol(2007) 60:19-26
[90]E De Palo,R Gatti,N Sicolo,et al.Plasma and urine free L-carnitine in human diabetes mellitus.Acta Diabetol Lat.1981:18(1):91-5.
[91]旷劲松,王福莉,李彦华,等.白碧玲肥胖症患者餐后利空腹血浆游离肉碱水平的检测及其意义[J]中国实用内科杂志,2004(24)2:97
[92]蔺小红,焦莉莉,徐国宾等.肝病患者血清肉碱水平的临床研究[J]中华肝脏病杂志,2006(14)5:367-369
[93]谷朵华,李铮,刘勇等.高效液相色谱法测定不育男子精浆左卡尼汀及其临床意义[J]中国男科学杂志,2005(19)1:48-49
[94]王福莉,刘国良.糖尿病伴冠心病患者血浆游离肉碱水平的相关性研究[J].中国误诊学杂志.2006,6(19):3687-3688
[95]赵亚明,王得新,吴丽娟等.脂肪累积性肌肉病患者血浆左旋肉碱含量测定的意义[J].中华神 经科杂志,2002(35):214-216
[96]赵亚明,刘古东,王得新.左旋肉碱治疗慢性疲劳综合征的研究[J].临床和实验医学杂志,2004,(3)3:133-135
[97]Takiyama N,Matsumoto K.Age-and sex-related differences of serum carnitine in a Japanese population.J Am Coll Nutr,1998,17:71-74
[98]RE Stevens,R Roy,KV Phelps.Evaluation of single- and multiple-dose pharmacokinetics of synthetic conjugated estrogens,A(Cenestin) tablets:a slow-release estrogen replacement product.J.Clin.Pharmacol.2002,42:332-341
[99]Yasuhito Fujisaka,Tomohide Tamura,Yuichiro Ohe,et al.Pharmacokinetics and Pharmacodynamics of Weekly Epoetin Beta in Lung Cancer Patients.Jpn J Clin Oncol 2006;36(8)477-482
[100]Wei Lu,Ph D,TGK Mant,et al.Pharmacokinetics of Recombinant Transgenic Antithrombin in Volunteers.Anesth Analg 2000;90:531-4
[101]John C,Roberts,Brent M,et al.Pharmacodynamic and Pharmacokinetic Studies of Agmatine after Spinal Administration in the Mouse.JPET,2005,314:1226-1233
[102]MATHIAS L,CLAUDE L,ALAIN B,et al.Bioavailability and Pharmacokinetics of Dehydroepiandrosterone in the Cynomolgus Monkey.J Clin Endocrinol Metab,2003,88(9):4293-4302
[103]GM Meno-Tetang,RA Blum,KE Schwartz,et al.Effects of oral prasterone (dehydroepiandrosterone) on single-dose pharmacokinetics of oral prednisone and cortisol suppression in normal women.J.Clin.Pharmacol.2001;41;1195-1205
[104]Robert H,Mathias L,Marianne SW,et al.Intranasal Loteprednol Etabonate in Healthy Male Subjects:Pharmacokinetics and Effects on Endogenous Cortisol.J.Clin.Pharmacol.2004;44;510-519
[105]James P.Thomas,Rhoda Z,et al.Phase I Pharmacokinetic and Pharmacodynamic Study of Recombinant Human Endostatin in Patients With Advanced Solid Tumors.Journal of Clinical Oncology,2003,21(2):223-231
[106]Amy E.Lovejoy,Tom C.Reynolds,Jennifer E,et al.Safety and pharmacokinetics of recombinant factor ⅩⅢ-A2 administration in patients with congenital factor ⅩⅢ deficiency.BLOOD,2006,108(1):57-62
[107]Gudjonsson H,Li B,Shug AL,et al.In vivo studies of intestinal carnitine absorption in rats.Gastroenterology 1985;88(6):1880-7.
[108]Rebouche CJ.Quantitative estimation of absorption and degradation of a carnitine supplement by human adults.Metabolism 1991;40(12):1305-10.
[1]J Kerner,C Hoppel.Generic disorders of carnitinemetabolism and their nutritional management [J].Annu Rev Nutr,1998,18:179-206.
[2]Reda E,Iddio D,Nicolai R,et al.The carnitine system and body composition[J].Acta Diabetol,2003,40(11):106-113.
[3]Mario M,Guido B,Gilusepppe C,et al.History of L-carnitine:Implications for renal disease[J].J Ren Nutr,2003,13(1):2-14.
[4]Giafranco G,Roberta S,Gianni B.Carnitine metabolism in uremia[J].Am J Kidney Dis,2001,38(4):63-67.
[5]Ramsay R.The carnitine acyltransferases:modulators of acyl-CoA-dependent reactions [J].Biochem SociTran,2000,28(2):182-186.
[6]Bahl JJ,Bressler R.The pharmacology of carnitine.Annu Rev Pharmacol Toxicol 1987;27:257-77
[7]Bremer J.The role of carnitine in cell metabolism.In:De Simone C,Famularo G,editors.Carnitine today.Austin:Landes Bioscience,1997:1-37
[8]Carter AL,Abney TO,Lapp DF.Biosynthesis and metabolism of carnitine.J Child Neurol 1995;10 Suppl.2:3-7
[9]Peluso G,Barbarisi A,Savica V,et al.Carnitine:an osmolyte that plays a metabolic role.J Cell Biochem 2000;80:1-10
[10]Angsten G,Cederblad G,Meurling S.Reference ranges for muscle carnitine concentration in children[J].Ann Clin Biochem,2003,,40(4):404-410.
[11]林锋.左卡尼汀在全肠外营养中的应用[J].中华胃肠外科杂志,2003,3(1):42-44.
[12]Marzo A,Martelli EA,Mancinelli A,et al.Protein binding of L-carnitine family components.Participants Papers(Special Issue No Ⅲ).Eur J Drug Metab Pharmacokinet 1991,364-8
[13]Hurot J,Cucherat M,Haugh M,et al.Effects of L-carnitine supplementation in maintenance hemodialysis patients:A system-atic review[J].J Am Soc Nephrol,2002,13(3):708-714.
[14]罗家琳,马培龙,张洪波.左卡尼汀治疗肾性贫血临床观察[J].中国血液净化,2003,2(10):565-566.
[15]Lango R,Smolenski R,Narkiewicz M,et al.Influence of L-carnitine and its derivatives on myocardial metabolism and function in ischemic heart disease and during cardiopulmonary bypass[J].Cardiovasc Res,2001,51(1):21-29.
[16]Zaugg C,M Spaniol,P Kaufmann,et al.Myocardial function and energymetabolism in carnitine deficient rats CMLS[J].CellMol Life Sci,2003,60(4):767-775.
[17]Nemoto S,Aoki M,Dehua C,et al.Effects of carnitine on cardiac function after cardioplegic ischemia in neonatal rabbit hearts.Ann Thorac Surg,2001,71(1):254-259.
[18]涂向际,魏世超等.贝康亭治疗62例有机磷中毒心肌损害临床观察[J].福建医学学杂志,2002,24(4):156.
[19]Diaz M,Lopez F,Hernandez F,et al.L-carnitine effects on chemical composition of plasma lipoproteins of rabbits fed with normal and high cholesterol diets[J].Lipids,2000,35(6):627-632.
[20]Eskandari G,Kandemir O,Polar G,et al.Serum L-carnitine levels and lipoprotein compositions in chronic viral hepatitis Patients[J].Clinbiochem,2000,34(5):431.
[21]Malaguarnera M,Pistone G,Astuto M,et al.L-carnitine in the treatment of mild or moderate hepatic encephalopathy[J].Dig Dis,2000,21,(3):271.
[22]杨金龙,夏子禹,游龙英,等.复方左卡尼汀治疗慢性病毒性肝炎[J].中国新药与临床杂,200,20(2):125-126.
[23]施健,刘芬,谢渭芬.左卡尼汀的临床应用[J].中国临床药学杂志,2005,14(2):128-130.
[24]林修,叶榕,王耀新.卡尼汀治疗急性脑梗死[J].中国新药与临床杂志,2001,20(2):121.
[25]Montgomery S,Thai L,Amrein R,et al.Meta-analysis of double-blind randomized controlled clinical trials of acetyl-L-carnitine versus placebo in the treatment of mild cognitive impairment and mild Alzheimer's disease[J].Int Clin Psychopharmacol,2003,18(2):61-71.
[26]Benvenga S,Ruggeri R,Russo A,et al.Usefulness of L-carnitine,a naturally accurally peripheral antagonist of thyroid hormone action in iatrogenic hyperthyroidism:a randomized,double-blind,placebo controlled clinical trial[J].J Clin Endocrinol Metab,2001,86(8):3579-3594.
[27]王咏梅,殷仁富,杜荣增,等.左旋卡尼汀对糖尿病伴高血压患者血浆左卡尼汀浓度及血糖的影响[J].第二军医大学学报,2003,24(4):425.
[28]Benvenga S,Lapa D,Canavo S,et al.Successive thyroid storms treated with L-carnitine and low doses of methimazole[J].Am J Med,2003,115(5):417.
[29]Malone J,Schocken D,Morrison A,et al.Diabetic cardiomyopa2 thy and carnitine deficiency[J].J Diabetes Complications,1999,13(2):86.
[30]Dahlstrom K,Ament M,Moukarzel A,et al.Low blood and plasma carnitine levels in children receiving long-term parenteral nutrition[J].J Pediatr Gastroenterol Nutr,1990,11(3):375-379.
[31]Tibboel D,De Lemarre F,Przyrembel H.et al.carnitine deficiency in surgical neonates receiving total parenteral nutrition[J].J Pediatr Surg,1990,25:418-421.
[32]Center S,Harte J,Watrous D,et al.The clinical and metabolic effects of rapid weight loss in obese pet cats and the influence of supplemental oral L-carnitine[J].J Vet InternMed,2000,14(6):598-608.
[33]Villani R,Gannon J,Self M,et al.L-Carnitine supplementation combined with aerobic training does not promote weight loss in moderately obese women[J].Int Sport Nutr Exerc Metab,2000,10(2):199-207.
[34]Agarwal A,Said T.Carnitines and male infertility[J].Reprod Biomed Online,2004,8(4):376-384.
[35]谷荣华等.高效液相色谱法测定不育男子精浆左卡尼汀及其临床意义[J].中国男科学杂志,2005,19(1):49.
[36]De Simone C,Moretti S,Marcellini S,et al.L-Carnitine a modulator of immunometabolic homeostasis in subjects infected with the human immunodeficiency virus.In:De Simone C,Famularo G,editors.Carnitine today.Austin:Landes Bioscience,1997:215-31
[37]Murakami K,Sugimoto T,Woo M,et al.Effect of L-carnitine supplementation on acute valproate intoxication.Epilepsia 1996;37(7):687-9
[38]Bohan TP,Helton E,McDonald I,et al.Effect of L-carnitine treatment for valproate-induced hepatotoxicity.Neurology 2001;56(2 of 2):1405-8
[39]Kelly GS.L-Carnitine:therapeutic applications of a conditionally-essential amino acid.Altern Med Rev 1998;3(5):345-60
[40]Travassos L.R.C.O.Sales.Microbiological assay of carnitine.Anal.Biochem,1974,58:485-499
[41]Friedman,S.Determination of carnitine in biological mat.erials.Arch.Biochem.Biophys,1958,75:24-31
[42]Fritz IB,Schulz SK,Srere PA.Properties of partially purified carnitine acetyltransferase.J Biol Chem 1963;238:2509-17
[43]Marquis NB,Fritz IB.Enzymological determination of free carnitine concentrations in rat tissue.J Lipid Res 1964;5:184-7
[44]Deufel T.Determination of L-carnitine in biological fluids and tissues.J Clin Chem Clin Biochem 1990;28(5):307-11
[45]陈肖燕,谢鑫友等.全自动酶法测定血清总合利游离卡尼汀浓度及临床应用[J].中华检验医学杂志,2003,26(12):764-767)
[46]Xia LJ,Folkers K.Improved methodology to assay carnitine and levels of free and total carnitine in human plasma.Biochem Biophys Res Commun 1991;176(3):1617-23
[47]Harper P,Elwin CE,Cederblad G.Pharmacokinetics of bolus intravenous and oral doses of L-carnitine in healthy subjects.Eur J Clin Pharmacol 1988;35:69-75
[48]Pearson DJ,Tubbs PK.A sensitive enzymic assay for carnitine.Biochem J 1964;91(1):2C-4C
[49]Wieland OH,Deufel T,Paetzke-Brunner I.Free and esterified carnitine -colorimetric method.In:Bergmeyer H,editor.Methods of enzymatic analysis.Weinheim:Verlag Chemic,1985:481-8
[50]Schafer,J.and Reichmann,H.A spectrophotometric method for the determination of free and esterified carnitine.Clinica Chimica Acta,1989,182:87-94.
[51]Williamson J.R,Schulz H,Fong J.C.Short-chain and long-chain enoyl-CoA hydratases from pig heart muscle[J],Methods Enzymology,1969,13:505-509
[52]Maehara M,Kinoshita S,Watanabe K.A simple fluorometric method for the determination of serum free carnitine.Clin Chim Acta.1988;171:311-316
[53]Mamoru Takahashi,Shigeru Ueda,Hideo Misaki,et al.Carnitine determination by an enzymatic cycling method with carnitine dehydrogenase.Clin.Chem,1994;40(5):817-821
[54]Cederblad G,Lindstedt S.A method for the determination of carnitine in the picomole range.Clin Chim Acta 1972;37:235-43
[55]Christiansen RZ,Bremer J.Acetylation of tris(hydroxymethy-1)aminomethane(tris) and tris derivatives by carnitine acetyl-transferase.FEBS Lett 1978;86(1):99-102
[56]Pace JA,Wannemacher RW,Neufeld HA.Improved radio-chemical assay for carnitine and its derivatives in plasma and tissue extracts.Clin Chem 1978;24(1):32-5
[57]Fishlock RC,Bieber LL,Snoswell AM.Sources of error in determinations of carnitine and acylcarnitine in plasma.Clin Chem 1984;30(2):316-8
[58]De Sousa C,English NR,Stacey TE,et al.Measurement of L-carnitine and acylcarnitine in body fluids and tissues in children and in adults.Clin Chim Acta 1990;187:317-28
[59]Kerner J,Bieber LL.A radioisotopic-exchange method for quantitation of short-chain (acid-soluble) acylcarnitines.Anal Biochem 1983;134:459-66
[60]Schmidt-Sommerfeld E,Penn D,Duran M,et al.Detection of inborn errors of fatty acid oxidation from acylcarnitine analysis of plasma and blood spots with the radioisotopic exchange-high-performance liquid chromatographic method.J Pediatr 1993;122(5 pt 1):708-14
[61]Schmidt-Sommerfeld E,Zhang L,Bobrowski P J,et al.Quantitation of short- and medium-chain acylcarnitines in plasma by radioisotopic exchange/high-performance liquid chromatography.Anal Biochem 1995;231(1):27-33
[62]Naoshi Takeyama,Yuji Iwanaga,Ken-ichi Kato,et al.Measurement of free and esterified carnitine in tissue extracts by high-performance liquid chromatography[J].Anal.Biochem,1986,158:346- 354
[63]Nobuhiko Arakawa,Yoshito Otake,Keisuke Hagio,et al.L-Carnitine Decreases Glycatin of Lens Proteins:in vitro studies[J].J.Nutr.Sci,Vitaminol,1989,35:475-479
[64]Minkler PE,Ingals ST,Hoppel CL.High-performance liquid chromatographic separation of acylcarnitines following derivatization with 4,'-bromophenacyl trifluoromethanesulfonate.Anal Biochem 1990;185:29-35
[65]Minkler PE,Hoppel CL.Quantification of free carnitine individual short-and medium-chain acylcarnitines and total carnitine in plasma by high-performance liquid chromatography.Anal Biochem 1993;212(2):510-8
[66]Minkler PE,Brass EP,Hiatt WR,et al.Quantification of carnitine,acetylcarnitine and total carnitine in tissues by high-performance liquid chromatography:the effect of exercise on carnitine homeostasis in man.Anal Biochem 1995;231:315-22
[67]Bhuiyan AK,Jackson S,Turnbull DM,et al.The measurement of carnitine and acyl-carnitine:application to the investigation of patients with suspected inherited disorders of mitochondrial fatty acid oxidation.Clin Chim Acta 1992;207(3):185-204
[68]Kamimori H,Hamashima Y,Konishi M.Determination of carnitine and saturated-acyl group carnitines in human urine by high-performance liquid chromatography with fluorescence detection.Anal Biochem 1994;218(2):417-27
[69]Longo A,Bruno G,Curti S,et al.Determination of L-carnitine acetyl-L-carnitine and propionyl-L-carnitine in human plasma by high-performance liquid chromatography after pre-column derivitization with l-aminoanthracene.J Chromatogr B Bi.omed Appl 1996;686(2):129-39
[70]冯一,张顺国等.HPLC法测定血清肉碱的研究[J].营养学报,2006,28(2):177-179;57
[71]丁峰,朱秋毓等.高效液相色谱法测定血.浆游离肉碱[J].药物分析杂志,2005,25(10):1195-1197
[72]邵秀芬.严琳等.离子对RP-HPLC法测定左卡尼汀片剂的含量[J].药学进展,2004,28(3):131-134
[73]单林,宋国华等.反相高效液相色谱法测定肉碱[J].中国公共卫生.2001,17(5):457-458
[74]赵榕,孙开奇.离子对反相高效液相色谱法测定保健食品中肉碱[J].中国食品卫生.2002,14(4):25-26
[75]Lowes S,Rose ME,Mills GA.Identification of urinary acyl-carnitines using gas chromatography-mass spectrometry:preliminary clinical applications.J Chromatogr 1992;577(2):205-14
[76]Huang ZH,Gage DA,Bieber LL,et al.Analysis of acyl-carnitines as their N-demethylated ester derivatives by gas chroma-tography-chemical ionization mass spectrometry.Anal Bio-chem 1991;199(1):98-105
[77]Millington DS,Roe CR,Maltby DA.Application of high resolution fast atom bombardment and constant B/E ration linked scanning to the identification and analysis of acylcarnitines in metabolic disease.Biomed Mass Spectrom 1984;11(5):236-41
[78]Yergey AL,Liberato D J,Millington DS.Thermospray liquid chromatography/mass spectrometry for the analysis of L-carnitine and its short-chain acyl derivatives.Anal Biochem 1984;139(2):278-83
[79]Norwood DL,Kodo N,Millington DS.Application of continuous-flow liquid chromatography/fast-atom bombardment mass spectrometry to the analysis of diagnostic acylcarnitines in human urine.Rapid Commun Mass Spectrom 1988;2(12):269-72
[80]Gaskell S J,Guenat C,Millington DS.Differentation of isomeric acylcarnitines using tandem mass spectrometry.Anal Chem 1986:,58(13):2801-5
[81]Johnson AW,Mills K,Clayton PT.The use of automated electrospray ionization tandem MS for the diagnosis of inborn errors of metabolism from dried blood spots.Biochem Soc Trans 1996;24(3):932-8
[82]Vreken P,Van Lint AE,Bootsma AH,et al.Quantitative plasma acylcarnitine analysis using electrospray tandem mass spectrometry for the diagnosis of organic acidaemias and fatty acid oxidation defects.J Inherit Metab Dis 1999;22(3):302-6
[83]Chace DH,DiPerna JC,Mitchell BL,et al.Electrospray tandem mass spectrometry for analysis of acylcarnitines in dried post-mortem blood specimens collected at autopsy from infants with unexplained cause of death.Clin Chem 2001;47(7):1166-82
[84]Wiley V,Carpenter K,Wilcken B.Newborn screening with tandem mass spectrometry:12months' experience in NSW Australia.Acta Paediatr Suppl 1999;88(432):48-51
[85]Naylor EW,Chace DH.Automated tandem mass spectrometry for mass newborn screening for disorders in fatty acid,organic acid and amino acid metabolism.J Child Neurol 1999;14 Suppl.1:S4-8
[86]Vaz FM,Wanders RJA.Carnitine biosynthesis in mammals.Biochem J 2002;361:417-29
[87]Lombard KA,Olson AL,Nelson SE,et al.Carnitine status of lactoovovegetarians and strict vegetarian adults and children.Am J Clin Nutr 1989;50(2):301-6
[88]Rebouche CJ.Carnitine function and requirements during the life cycle.FASEB J 1992 Dec;6:3379-86
[89]Rebouche CJ.Metabolic fate of dietary carnitine in humans.In:Lee Carter A,editor.Current concepts in carnitine research.Boca Raton & Ann Arbor:CRC Press,1992:37-48
[90]Cederblad G.Effect of diet on plasma carnitine levels and urinary carnitine excretion in humans.Am J Clin Nutr 1987;45(4):725-9
[91] Wiley V, Carpenter K, Wilcken B. Newborn screening with tandem mass spectrometry: 12 months' experience in NSW Australia. Acta Paediatr Suppl 1999; 88 (432): 48-51
[92] Rebouche CJ, Seim H. Carnitine metabolism and its regulation in microorganisms and mammals.AnnuRevNutr 1998; 18:39-61
[93] Bieber LL. Carnitine. Annu Rev Biochem 1988; 57: 261-833
[94] Rebouche CJ, Chenard CA. Metabolic fate of dietary carnitine in human adults: identification and quantification of urinary and fecal metabolites. J Nutr 1991; 121 (4): 539-46
[95] Rebouche CJ, Lombard KA, Chenard CA. Renal adaptation to dietary carnitine in humans. Am J Clin Nutr 1993; 58: 660-5
[96] Mancinelli A, Longo A, Shanahan K, et al. Disposition of L-carnitine and acetyl-L-carnitine in the isolated perfused rat kidney. J Pharmacol Exp Ther 1995; 274 (3): 1122-8
[97] Marzo A, Martelli EA, Mancinelli A, et al. Protein binding of L-carnitine family components.Participants Papers (Special Issue No III). Eur J Drug Metab Pharmacokinet 1991, 364-8
[98] Frolich J, Seccombe DW, Hahn P, et al. Effect of fasting on free and esterified carnitine levels in human serum and urine: correlation with serum levels of free fatty acids and b-hydrox-ybutyrate.Metabolism 1978; 27 (5): 555-61
[99] Engel AG, Rebouche CJ, Wilson DM, et al. Primary systemic carnitine deficiency: II. renal handling of camitine. Neurology 1981; 31: 819-25
[100] Stanley CA, Berry GT, Bennett MJ, et al. Renal handling of carnitine in secondary carnitine deficiency disorders. Pediatr Res 1993; 34: 89-97
[101] Bernardini I, Rizzo WB, Dalakas M, et al. Plasma and muscle free carnitine deficiency due to renal Fanconi syndrome. J Clin Invest 1985; 75: 1124-30
[102] Ohashi R, Tamai I, Nezu J, et al. Molecular and physiological evidence for multifunctionality of camitine/organic cation transporter OCTN2. Mol Pharmacol 2001; 59 (2): 358-66
[103] Tamai I, Ohashi R, Nezu J, et al. Molecular and functional identification of sodium ion-dependent, high affinity human carnitine transporter OCTN2. J Biol Chem 1998; 273(32):20378-82
[104] Wagner CA, Lukewille U, Kaltenbach S, et al. Functional and pharmacological characterization of human Na+-carnitine cotransporter hOCTN2. Am J Physiol Renal Physiol 2000; 279:F584-91
[105] Wang Y, Ye J, Ganpathy V, et al. Mutations in the organic cation/ carnitine transporter OCTN2 in primary carnitine deficiency. Proc Natl Acad Sci U S A 1999; 96: 2356-60
[106] Wu X, Huang W, Prasad PD, et al. Functional characteristics and tissue distribution pattern of organic cation transporter 2(OCTN2), an organic cation/carnitine transporter. J Pharmacol Exp Ther 1999; 290: 1482-92;
[107] Nezu J, Tamai I, Oku A, et al. Primary systemic carnitine deficiency is caused by mutations in a gene encoding sodium ion-dependent carnitine transporter. Nat Genet 1999; 21 (1):91-4
[108] Tang NL, Ganpathy V, Wu X, et al. Mutations of OCTN2, an organic cation/carnitine transporter, lead to deficient cellular carnitine uptake in primary carnitine deficiency. Hum Mol Genet 1999; 8: 655-60
[109] Angelini C, Vergani L, Martinuzzi A. Clinical and biochemical aspects of carnitine deficiency and insufficiency: transport defects and inborn errors of -oxidation. Crit Rev Clin Lab Sci 1992; 29 (3-4): 217-42
[110] Pons R, De Vivo DC. Primary and secondary carnitine deficiency syndromes. J Child Neurol 1995;10 Suppl.2:2S8-24
[111] Angelini C, Vergani L, Martinuzzi A. Clinical and biochemical aspects of carnitine deficiency and insufficiency: transport defects and inborn errors of -oxidation. Crit Rev Clin Lab Sci 1992; 29 (3-4): 217-42
[112] Bertoli M, Battistella PA, Vergani L, et al. Carnitine deficiency induced during hemodialysis and hyperlipidemia: effect of replacement therapy. Am J Clin Nutr 1981; 34: 1496-500
[113] Moorthy AV, Rosenblum M, Rajaram R, et al. A comparison of plasma and muscle carnitine levels in patients on peritoneal or hemodialysis for chronic renal failure. Am J Nephrol 1983;3:205-8;
[114] Brooks DE. Carnitine in the male reproductive tract and its relation to the metabolism of the epididymis and spermatozoa.In: Frenkel R, McGarry J, editors. Carnitine biosynthesis metabolism and function. New York: Academic Press, 1980:219-35
[115] Brass EP. Pharmacokinetic considerations for the therapeutic use of carnitine in hemodialysis patients. Clin Ther 1995; 17(2): 176-85
[116] Bellinghieri G, Savica V, Mallamace A, et al. Correlation between increased serum and tissue L-carnitine levels and improved muscle symptoms in hemodialyzed patients. Am J Clin Nutr 1983; 38:523-31
[117]Wanner C, Horl WH. Carnitine abnormalities in patients with renal insufficiency:pathophysiological and therapeutical aspects. Nephron 1988; 50: 89-102
[118] Famularo G, Matricardi F, Nucera E, et al. Carnitine deficiency: primary and secondary syndromes. In: De Simone C, Famularo G, editors. Carnitine today. Austin: Landes Bioscience,1997:119-61
[119]Cooper MB, Forte CA, Jones DA. Carnitine and acetylcarnitine in red blood cells. Biochim Biophys Acta 1988; 959: 100-5
[120] Gudjonsson H, Li B, Shug AL, et al. In vivo studies of intestinal carnitine absorption in rats.Gastroenterology 1985; 88 (6): 1880-7
[121] Matsuda K, Yuasa H, Watanabe J. Physiological mechanism based analysis of dose-dependent gastrointestinal absorption of L-carnitine in rats. Biopharm Drug Dispos 1998; 19: 465-72
[122] Matsuda K, Yuasa H, Watanabe J. Fractional absorption of L-carnitine after oral administration in rats: evaluation of absorption site and dose dependency. Biol Pharm Bull 1998; 21 (7):752-5
[123] Gross CJ, Henderson LM, Savaiano DA. Uptake of L-carnitine,D-carnitine and acetyl-L-carnitine by isolate guinea-pig enter ocytes. Biochim Biophys Acta 1986; 886: 425-33
[124] Shaw RD, Li B, Hamilton JW, et al. Carnitine transport in rat small intestine. Am J Physiol 1983;245:G376-81
[125] Hamilton JW, Li B, Shug AL, et al. Carnitine transport in human intestinal biopsy specimens:demonstration of an active transport system. Gastroenterology 1986; 91 (1): 10-6
[126] McCloud E, Ma TY, Grant KE, et al. Uptake of L-carnitine by human intestinal epithelial cell line, Caco 2. Gastroenterology 1996; 111 (6): 1534-40
[127] Gross CJ, Henderson LM. Absorption of D- and L-carnitine by the intestine and kidney tubule in the rat. Biochim Biophys Acta 1984; 772: 209-19
[128] Sahajwalla CG, Helton ED, Punch ED, et al. Multiple-dose pharmacokinetics and bioequivalence of L-carnitine 330mg tablet versus 1g chewable tablet versus enteral solution in healthy adult male volunteers. J Pharm Sci 1995; 84 (5):627-33
[129] Segre G, Bianchi E, Corsi M, et al. Plasma and urine pharmacokinetics of free and of short-chain carnitine after administration of carnitine in man. Arzneimittel Forschung 1988; 38 (II)(12):1830-4
[130] Harper P, Elwin CE, Cederblad G. Pharmacokinetics of bolus intravenous and oral doses of L-carnitine in healthy subjects. Eur J Clin Pharmacol 1988; 35: 69-75
[131] Rizza V, Lorefice R, Rizza N, et al. Pharmacokinetics of L-carnitine in human subjects. In:Ferrari R, Dimauro S, Sher wood G, editors. L-Carnitine and its role in medicine: from function to therapy. New York: Academic Press, 1992: 63-77
[132] Borum PR. Plasma carnitine compartment and red blood cell carnitine compartment of healthy adults.Am J Clin Nutr,1987,46:437-441
[133] Sahajwalla CG, Helton ED, Purich ED, et al. Comparison of L-carnitine pharmacokinetics with and without baseline correction following administration of single 20mg/kg intravenous dose. J Pharm Sci 1995;84(5):634-9
[134] Rebouche CJ, Engel AG. Kinetic compartmental analysis of carnitine metabolism in the human carnitine deficiency syndromes. J Clin Invest 1984 Mar; 73 (3): 857-67
[135] Dippenaar N, Clauss RP, Feinendegen LE. Effect of carnitine and essential fatty acid supplementation on the uptake of 11C-carnitine in muscle of a myopathic carnitine-deficient patient using positron emission scintigraphy. Prostaglandins Leukot Essent Fatty Acids 1998; 58(3): 201-4
[136] Brooks DE, McIntosh JE. Turnover of carnitine by rat tissues. Biochem J 1975; 148 (3): 439-45
[137] Cederblad G, Lindstedt S. Metabolism of labeled carnitine in the rat. Arch Biochem Biophys 1976; 175: 173-80;
[138] Rebouche C, Engel A. Kinetic compartmental analysis of carnitine metabolism in the dog. Arch Biochem Biophys 1983; 220:60-70
[139] Khairallah EA, Wolf G. Carnitine decarboxylase: the conversion of carnitine to-methylcholine. J Biol Chem 1967; 242(1): 32-9
[140] Rebouche CJ. Quantitative estimation of absorption and degradation of a carnitine supplement by human adults. Metabolism 1991; 40 (12): 1305-10
[141] Zhang AQ, Mitchell SC, Smith RL. Discontinuous distribution of n-oxidation of dietary-derived trimethylamine in a British population. Xenobiotica 1996; 26 (9): 957-61
[142] Zhang AQ, Mitchell SC, Smith RL. Dietary precursors of trimethylamine in man: a pilot study.Food Chem Toxicol 1999; 37: 515-20
[143] Ayesh R, Mitchell SC, Zhang A, et al. The fish odour syndrome: biochemical familial and clinical aspects. BMJ 1993;307 (6905): 655-7
[144] Humbert JR, Hammond KB, Hathaway WE, et al. Trimethy-laminuria: the fish-odour syndrome.Lancet 1970; II(7676):770-l
[145] Mitchell SC. The fish-odour syndrome. Perspect Biol Med 1996; 39 (4): 514-26
[146] Mitchell SC, Zhang AQ, Smith RL. Fish-odour syndrome and impaired n-oxidation. Biochem Soc Trans 1996; 24(1): 965
[147] Al-Waiz M, Ayesh R, Mitchell SC, et al. Disclosure of the metabolic retroversion of trimethylamine N-oxide in humans:a pharmacogenetic approach. Clin Pharmacol Ther 1987;42(6): 608-12
[148] Zeisel S, Da Costa K, Ox J. Endogenous formation of dimethylamine.Biochem J 1975; 232 (2):403-8
[149] Mitchell SC, Zhang A, Smith RL, et al. Trimethylamine noxide as a probable source of urinary dimethylamine in man; a statistical approach. Biochem Soc Trans 1998; 26 (2): S182
[150] Zhang AQ, Mitchell SC, Ayesh R, et al. Dimethylamine formation in man. Biochem Pharmacol 1993; 45 (11): 2185-8
[151] Sahajwalla CG, Helton ED, Purich ED, et al. Multiple-dose pharmacokinetics and bioequivalence of L-carnitine 330mg tablet versus 1g chewable tablet versus enteral solution in healthy adult male volunteers. J Pharm Sci 1995; 84 (5):627-33
[152] Hokland BM, Bremer J. Metabolism and excretion of carnitine and acylcarnitines in the perfused rat kidney. Biochim Biophys Acta 1986; 886 (2): 223-30
[153] Rebouche CJ, Engel AG. Carnitine metabolism and deficiency syndrome. Mayo Clin Proc 1983 Aug; 58: 533-40
[154] Pons R, Carrozzo R, Tein I, et al. Deficient muscle carnitine transport in primary carnitine deficiency. Pediatr Res 1997; 42:583-7
[155] Rebouche CJ, Paulson DJ. Carnitine metabolism and function in humans. Annu Rev Nutr 1986;6: 41-66
[156] Rose SJ, Stokes TC, Patel S, et al. Carnitine deficiency associated with long-term pivampicillin treatment: the effect of a replacement therapy regime. Postgrad Med J 1992; 68: 932-4
[157] Holme E, Jodal U, Linstedt S, et al. Effects of pivalic acid containing prodrugs on carnitine homeostasis and on response to fasting in children. Scand J Clin Lab Invest 1992; 52 (5):361-72
[158] Dalakas MC, Leon-Monzon ME, Bernardini I, et al. Zidovu-dine-induced mitochondrial myopathy is associated with muscle carnitine deficiency and lipid storage. Ann Neurol 1994; 35(4): 482-7
[159] Ross NS, Hoppel CL. Partial muscle carnitine palmitoyltrans-ferase-A deficiency. JAMA 1987;257(1): 62-5
[160] Ganapathy V, Huang W, Rajan DP, et al. Beta-lactam antibiotics as substrates for OCTN2, an organic cation/carnitine transporter. J Biol Chem 2000; 275 (3): 1699-707
[161] Ohtani Y, Nishiyama S, Matsuda I. Renal handling of free and acylcarnitine in secondary carnitine deficiency. Neurology 1984; 34 (7): 977-9
[162] Krahenbuhl S, Reichen J. Carnitine metabolism in patients with chronic liver disease. Hepatology 1996;25: 148-53
[163] Bartel LL, Hussey JL, Shrago E. Perturbation of serum carnitine levels in human adults by chronic renal disease and dialysis therapy. Am J Clin Nutr 1981 Jul; 34: 1314-20
[164] Rodriguez-Segade S, de la Pe~na CA, Paz M, et al. Carnitine concentrations in dialysed and undialysed patients with chronic renal insufficiency. Ann Clin Biochem 1986; 23: 671-5
[165] Ahmad S. Carnitine, kidney and renal dialysis: carnitine and the kidney. In: Ferrari R, Dimauro S, Sherwood G, editors. L-Carnitine and its role in medicine: from function to therapy. New York: Academic Press, 1992: 381-400
[166] Bohmer T, Bergrem H, Eiklid K. Carnitine deficiency induced during intermittent haemodialysis for renal failure. Lancet 1978; I (8056): 126-8
[167] Perm D, Schmidt-Sommerfeld E. Carnitine and carnitine esters in plasma and adipose tissue of chronic uremic patients under, going hemodialysis. Metabolism 1983; 32 (8): 806-9
[168] Vacha GM, Corsi M, Giorcelli G, et al. Serum and muscle L-carnitine levels in hemodialyzed patients during and after long-term L-carnitine treatment. Curr Ther Res 1985; 37 (3): 505-16
[169]. Jackson JM, Lee HA. L-Carnitine and acetyl-L-carnitine status during hemodialysis with acetate in humans: a kinetic analysis. Am J Clin Nutr 1996; 64: 922-7
[170]Guarnieri G,Toigo G,Crapesi L,et al.carnitine metabolism in chronic renal failure.Kidney Int Suppl 1987;32 Suppl.22:S116-27
[171]Sakurauchi Y,Matsumoto Y,Shinzato T,et al.Effects of L-carnitine supplementation on muscular symptoms in hemodi-alyzed patients.Am J Kidney Dis 1998;32(2):258-64
[172]Golper TA,Wolfson M,Ahmad S,et al.Multicenter trial of Lcarnitine in maintenance hemodialysis patients:I.carnitine concentrations and lipid effects.Kidney Int 1990;38:904-11
[173]Siami G,Clinton ME,Mrak R,et al.Evaluation of the effect of intravenous L-carnitine therapy on function structure and fatty acid metabolism of skeletal muscle in patients receiving chronic hemodialysis.Nephron 1991;57:306-13
[174]Savica V,Bellinghieri G,Di Stefano C,et al.Plasma and muscle carnitine levels in haemodialysis patients with morpho-logical-ultrastructural examination of muscle samples.Nephron 1983;35:232-6
[175]Debska-Slizien A,Kawecka A,Wojnarowski K,et al.Correlation between plasma carnitine muscle carnitine and glycogen levels in maintenance hemodialysis patients.Int J Artif Organs 2000;23(2):90-6;
[176]Evans AM,Faul R,Fornasini G,et al.Pharmacokinetics of L-carnitine in patients with end-stage renal disease undergoing long-term hemodialysis.Clin Pharmacol Ther 2000;68(3):238-49
[177]刘慧兰,张晓沾,等.血液透析患者静脉静脉应用左旋肉碱(可益能)的药代动力学研究.[J]中国血液挣化,2003,2(6):298-310
[178]Savica V,Bellinghieri G,Di Stefano C,et al.Plasma and muscle carnitine levels in haemodialysis patients with morpho-logical-ultrastructural examination of muscle samples.Nephron 1983;35:232-6