小檗碱对大鼠口服阿托伐他汀钙药代动力学的影响
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摘要
目的研究小檗碱对大鼠口服阿托伐他汀钙药代动力学的影响,为临床联合用药提供参考依据。方法大鼠随机分为5组,单次阿托伐他汀钙组(A组)、单次小剂量小檗碱+阿托伐他汀钙组(B组)、单次大剂量小檗碱+阿托伐他汀钙组(C组)、多次小剂量小檗碱+单次阿托伐他汀钙组(D组)及多次大剂量小檗碱+单次阿托伐他汀钙组(E组)。给药前后眼眶采血,采用HPLC法测定大鼠体内阿托伐他汀钙的浓度。经DAS 2.0药动学软件处理,获得各组药动学参数。结果大鼠在单次及多次灌胃不同剂量的小檗碱后,阿托伐他汀钙的体内药代动力学参数改变无统计学意义。结论正常用量下小檗碱对大鼠阿托伐他汀钙的药代动力学有一定的影响,但无统计学意义,在人体内的影响仍需进一步研究。
Objective To study the effect of berberine on the pharmacokinetics of atorvastatin calcium in rats,and provide a reference for the combination use of berberine and atorvastatin calcium.Methods Rats were randomly divided into 5 groups:group A was treated with single atorvastatin calcium,group B was treated with single low-dose berberine+atorvastatin calcium,group C with single high-dose berberine+atorvastatin calcium,group D with multiple low-dose berberine+single atorvastatin calcium,group E with multiple high-dose berberine+single atorvastatin calcium.Blood was collected from the eyelids before and after administration,and the concentration of atorvastatin calcium in rats was determined by HPLC.The data was processed by DAS 2.0 pharmacokinetic software to obtain pharmacokinetic parameters for each group.Results The pharmacokinetic parameters of atorvastatin calcium had no statistically significant change after single and multiple different doses of berberine by gavage in rats.Conclusion Berberine at normal dose has a certain effect on the pharmacokinetics of atorvastatin calcium in rats but there′s no statistical significance,further research is needed in humans.
Objective To study the effect of berberine on the pharmacokinetics of atorvastatin calcium in rats,and provide a reference for the combination use of berberine and atorvastatin calcium.Methods Rats were randomly divided into 5 groups:group A was treated with single atorvastatin calcium,group B was treated with single low-dose berberine+atorvastatin calcium,group C with single high-dose berberine+atorvastatin calcium,group D with multiple low-dose berberine+single atorvastatin calcium,group E with multiple high-dose berberine+single atorvastatin calcium.Blood was collected from the eyelids before and after administration,and the concentration of atorvastatin calcium in rats was determined by HPLC.The data was processed by DAS 2.0 pharmacokinetic software to obtain pharmacokinetic parameters for each group.Results The pharmacokinetic parameters of atorvastatin calcium had no statistically significant change after single and multiple different doses of berberine by gavage in rats.Conclusion Berberine at normal dose has a certain effect on the pharmacokinetics of atorvastatin calcium in rats but there′s no statistical significance,further research is needed in humans.
引文
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[22]Kwon M,Choi YA,Choi MK,et al.Organic cation transporter-mediated drug-drug interaction potential betw een berberine and metformin[J].Arch Pharm Res,2015,38(5):849-856.
[23]Liu M,Su X,Li G,et al.Validated UPLC-MS/MS method for simultaneous determination of simvastatin,simvastatin hydroxy acid and berberine in rat plasma:application to the drug-drug pharmacokinetic interaction study of simvastatin combined w ith berberine after oral administration in rats[J].J Chromatogr B Analyt Technol Biomed Life Sci,2015,1006:8-15.
[2]Gao F,Zhou YJ,Hu DY,et al.Contemporary management and attainment of cholesterol targets for patients w ith dyslipidemia in China[J].PLoS One,2013,8(4):e47681.
[3]Nash DB.The Use of medicines in the United States:a detailed review[J].Am Health Drug Benefits,2012,5(7):423.
[4]Imenshahidi M,Hosseinzadeh H.Berberis vulgaris and berberine:an update review[J].Phytother Res,2016,30(11):1745-1764.
[5]Kong W,Wei J,Abidi P,et al.Berberine is a novel cholesterol-low ering drug w orking through a unique mechanism distinct from statins[J].Nat M ed,2004,10(12):1344-1351.
[6]Cicero AF,Baggioni A.Berberine and its role in chronic disease[J].Adv Exp M ed Biol,2016,928:27-45.
[7]沈金花,尚文斌.阿托伐他汀联合黄连素对糖尿病合并脑梗死患者治疗效果的临床研究[J].医学理论与实践,2016,29(9):1121-1123.
[8]王强,苑晓春.盐酸小檗碱联合阿托伐他汀治疗急性脑梗死的疗效及对颈动脉粥样硬化斑块的影响[J].中国实用神经疾病杂志,2015,18(22):20-21.
[9]吴威.盐酸小檗碱联合阿托伐他汀治疗急性脑梗死的疗效及对颈动脉粥样硬化斑块的影响[J].中国老年学杂志,2016,36(18):4459-4460.
[10]Guo Y,Chen Y,Tan ZR,et al.Repeated administration of berberine inhibits cytochromes P450 in humans[J].Eur J Clin Pharmacol,2012,68(2):213-217.
[11]Chatterjee P,Franklin MR.Human cytochrome P450 inhibition and metabolic-intermediate complex formation by goldenseal extract and its methylenedioxyphenyl components[J].Drug M etab Dispos,2003,31(11):1391-1397.
[12]Qiu W,Jiang XH,Liu CX,et al.Effect of berberine on the pharmacokinetics of substrates of CYP3A and P-gp[J].Phytother Res,2009,23(11):1553-1558.
[13]Cui HM,Zhang QY,Wang JL,et al.In vitro studies of berberine metabolism and its effect of enzyme induction on HepG2cells[J].J Ethnopharmacol,2014,158 Pt A:388-396.
[14]Maeng HJ,Yoo HJ,Kim IW,et al.P-glycoprotein-mediated transport of berberine across Caco-2 cell monolayers[J].JPharm Sci,2002,91(12):2614-2621.
[15]Drug Bank Database.Accession Number DB01076[EB/OL].[2018-6-1].http://www.drugbank.ca/drugs/DB01076.
[16]Choi DH,Shin WG,Choi JS.Drug interaction between oral atorvastatin and verapamil in healthy subjects:effects of atorvastatin on the pharmacokinetics of verapamil and norverapamil[J].Eur J Clin Pharmacol,2008,64(5):445-449.
[17]Etheridge AS,Black SR,Patel PR,et al.An in vitro evaluation of cytochrome P450 inhibition and P-glycoprotein interaction w ith goldenseal,Ginkgo biloba,grape seed,milk thistle,and ginseng extracts and their constituents[J].Planta M ed,2007,73(8):731-741.
[18]邓建伟,郭栋,周宏灏.他汀类降血脂药物的药代动力学研究进展[J].中国临床药理学与治疗学,2007,12(8):850-860.
[19]SZK R,Rameshrad M,Hosseinzadeh H.Toxicology effects of Berberis vulgaris(barberry)and its active constituent,berberine:a review[J].Iran J Basic M ed Sci,2017,20(5):516-529.
[20]李晖,柴煊,李新芳.黄连素临床新用途及其不良反应[J].武警医学,2008,19(7):661-663.
[21]Cui H,Wang J,Zhang Q,et al.In vivo and in vitro study on drug-drug interaction of lovastatin and berberine from pharmacokinetic and HepG2 cell metabolism studies[J].M olecules,2016,21(4):464.
[22]Kwon M,Choi YA,Choi MK,et al.Organic cation transporter-mediated drug-drug interaction potential betw een berberine and metformin[J].Arch Pharm Res,2015,38(5):849-856.
[23]Liu M,Su X,Li G,et al.Validated UPLC-MS/MS method for simultaneous determination of simvastatin,simvastatin hydroxy acid and berberine in rat plasma:application to the drug-drug pharmacokinetic interaction study of simvastatin combined w ith berberine after oral administration in rats[J].J Chromatogr B Analyt Technol Biomed Life Sci,2015,1006:8-15.