万古霉素在超重、肥胖患儿中的给药方案及药物监测的Meta分析
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摘要
目的系统评价超重、肥胖患儿中万古霉素给药方案及治疗药物监测的结果,研究超重、肥胖患儿万古霉素临床使用情况及体内药动学特点,为临床超重、肥胖患儿合理使用万古霉素提供指导。方法系统检索英文数据库PubMed、Embase、Cochranelibrary、ClinicalTrials.gov及中文数据库中国知网和万方医学网关于万古霉素在超重、肥胖患儿人群中的相关临床研究文献,检索时间从建库至2017年12月,按照纳入和排除标准筛选文献、提取资料并进行描述性分析。结果共7篇研究纳入系统评价。结果显示,超重、肥胖患儿万古霉素多基于实际体重给药,给药间隔为6h或8h更容易使血药浓度达到10～20mg/L。1篇研究报道超重、肥胖患儿与正常体重患儿肾毒性发生率无统计学差异。万古霉素清除率在超重、肥胖患儿显著性增加,半衰期有增加的趋势,表观分布容积没有明显变化。结论万古霉素在超重、肥胖患儿中的给药方案还需要进一步研究,且万古霉素在该人群体内过程存在较大的个体差异,需要进行治疗药物监测指导给药。
Objective To systematically evaluate the results of therapeutic drug monitoring and study dosing regimens and the pharmacokinetics characteristics of overweight and obese pediatric patients. Methods PubMed, EMbase, Cochrane library, ClinicalTrials.gov, China National Knowledge Internet(CNKI), and WanFang databases were searched from the database setting up time to December 2017. The clinical studies which included overweight and obese pediatric patients using vancomycin intravenously were identified and screened according to the inclusion and exclusion criteria. The data were extracted and descriptively analyzed. Results Totally seven studies were included. In recent studies, vancomycin dosing regimens were based on total body weight and dosing intervals of six hours and eight hours might achieve the target trough concentration of 10～20 mg/L. One study demonstrated no statistical difference between the obsess and normal weight groups in the rate of nephrotoxicity. Compared with the normal weight group, clearance(CL) has increased significantly, and half life(T1/2) has increased tendency in overweight and obsess pediatric patients. However, the volume of distribution(Vd) showed no statistical difference. Conclusion Vancomycin dosing regimens require further evaluation and the pharmacokinetics have individual difference. Therapeutic drug monitoring is needed for overweight and obsess pediatric patients to guide the therapy and warrant the safety of vancomycin.
Objective To systematically evaluate the results of therapeutic drug monitoring and study dosing regimens and the pharmacokinetics characteristics of overweight and obese pediatric patients. Methods PubMed, EMbase, Cochrane library, ClinicalTrials.gov, China National Knowledge Internet(CNKI), and WanFang databases were searched from the database setting up time to December 2017. The clinical studies which included overweight and obese pediatric patients using vancomycin intravenously were identified and screened according to the inclusion and exclusion criteria. The data were extracted and descriptively analyzed. Results Totally seven studies were included. In recent studies, vancomycin dosing regimens were based on total body weight and dosing intervals of six hours and eight hours might achieve the target trough concentration of 10～20 mg/L. One study demonstrated no statistical difference between the obsess and normal weight groups in the rate of nephrotoxicity. Compared with the normal weight group, clearance(CL) has increased significantly, and half life(T1/2) has increased tendency in overweight and obsess pediatric patients. However, the volume of distribution(Vd) showed no statistical difference. Conclusion Vancomycin dosing regimens require further evaluation and the pharmacokinetics have individual difference. Therapeutic drug monitoring is needed for overweight and obsess pediatric patients to guide the therapy and warrant the safety of vancomycin.
引文
[1]央视网.《中国儿童肥胖报告》:7岁儿童肥胖率约为7.3%[EB/OL].(2017-05-12)[2018-12-26]http://news.cctv.com/2017/05/12/ARTIh4dkLQf8vMp5QI9dEcx3170512.shtml
[2]Cheymol G.Effects of obesity on pharmacokinetics implications for drug therapy[J].Clin Pharmacokinet,2000,39(3):215-231.
[3]Neely M,Louie S.Obesity and its impact on drug therapy[J].Clin Pharmacokinet,2011,50(12):825-826.
[4]Miller M,Miller J L,Hagemann T M,et al.Vancomycin dosage in overweight and obese children[J].Am J Health Syst Pharm,2011,68(21):2062-2068.
[5]Moffett B S,Kim S,Edwards M S,et al.Vancomycin dosing in obese pediatric patients[J].Clin Pediatr(Phila),2011,50(5):442-446.
[6]Nassar L,Hadad S,Gefen A,et al.Prospective evaluation of the dosing regimen of vancomycin in children of different weight categories[J].Curr Drug Saf,2012,7(5):375-381.
[7]Heble D E,Mcpherson C,Nelson M P,et al.Vancomycin trough concentrations in overweight or obese pediatric patients[J].Pharmacotherapy,2013,33(12):1273-1277.
[8]Eiland L S,Sonawane K B.Vancomycin dosing in healthyweight,overweight,and obese pediatric patients[J].JPediatr Pharmacol Ther,2014,19(3):182-188.
[9]Le J,Capparelli E V,Wahid U,et al.Bayesian estimation of vancomycin pharmacokinetics in obese children:Matched case-control study[J].Clin Ther,2015,37(6):1340-1351.
[10]Mahmoud M A,Ebid A H,Shouman S A,et al.Pharmacokinetics of vancomycin in oncology Egyptian paediatrics:A dosage adjustment trial[J].Ind J Pharm Sci,2014,76(1):82-86.
[11]Madigan T,Sieve R M,Graner K K,et al.The effect of age and weight on vancomycin serum trough concentrations in pediatric patients[J].Pharmacotherapy,2013,33(12):1264-1272.
[12]Xiong Y,Fukuda T,Knibbe C A J,et al.Drug dosing in obese children:Challenges and evidence-based strategies[J].Pediatr Clin North Am,2017,64(6):1417-1438.
[13]Rybak M,Lomaestro B,Rotschafer J C,et al.Therapeutic monitoring of vancomycin in adult patients:A consensus review of the American society of health-system pharmacists,the infectious diseases society of America,and the society of infectious diseases pharmacists[J].Am JHealth Syst Pharm,2009,66(1):82-98.
[14]Ye Z K,Chen Y L,Chen K,et al.Therapeutic drug monitoring of vancomycin:A guideline of the division of therapeutic drug monitoring,Chinese Pharmacological Society[J].J Antimicrob Chemother,2016,71(11):3020-3025.
[15]Gordon C L,Thompson C,Carapetis J R,et al.Trough concentrations of vancomycin:adult therapeutic targets are not appropriate for children[J].Pediatr Infect Dis J,2012,31(12):1269-1271.
[16]Le J,Bradley J S,Murray W,et al.Improved vancomycin dosing in children using area under the curve exposure[J].Pediatr Infect Dis J,2013,32(4):155-163.
[17]叶志康,陈恳,Pleasants R A,等.万古霉素血药谷浓度和临床结局相关性的系统评价和Meta分析[J].药物流行病学杂志,2016,25(4):197-208.
[2]Cheymol G.Effects of obesity on pharmacokinetics implications for drug therapy[J].Clin Pharmacokinet,2000,39(3):215-231.
[3]Neely M,Louie S.Obesity and its impact on drug therapy[J].Clin Pharmacokinet,2011,50(12):825-826.
[4]Miller M,Miller J L,Hagemann T M,et al.Vancomycin dosage in overweight and obese children[J].Am J Health Syst Pharm,2011,68(21):2062-2068.
[5]Moffett B S,Kim S,Edwards M S,et al.Vancomycin dosing in obese pediatric patients[J].Clin Pediatr(Phila),2011,50(5):442-446.
[6]Nassar L,Hadad S,Gefen A,et al.Prospective evaluation of the dosing regimen of vancomycin in children of different weight categories[J].Curr Drug Saf,2012,7(5):375-381.
[7]Heble D E,Mcpherson C,Nelson M P,et al.Vancomycin trough concentrations in overweight or obese pediatric patients[J].Pharmacotherapy,2013,33(12):1273-1277.
[8]Eiland L S,Sonawane K B.Vancomycin dosing in healthyweight,overweight,and obese pediatric patients[J].JPediatr Pharmacol Ther,2014,19(3):182-188.
[9]Le J,Capparelli E V,Wahid U,et al.Bayesian estimation of vancomycin pharmacokinetics in obese children:Matched case-control study[J].Clin Ther,2015,37(6):1340-1351.
[10]Mahmoud M A,Ebid A H,Shouman S A,et al.Pharmacokinetics of vancomycin in oncology Egyptian paediatrics:A dosage adjustment trial[J].Ind J Pharm Sci,2014,76(1):82-86.
[11]Madigan T,Sieve R M,Graner K K,et al.The effect of age and weight on vancomycin serum trough concentrations in pediatric patients[J].Pharmacotherapy,2013,33(12):1264-1272.
[12]Xiong Y,Fukuda T,Knibbe C A J,et al.Drug dosing in obese children:Challenges and evidence-based strategies[J].Pediatr Clin North Am,2017,64(6):1417-1438.
[13]Rybak M,Lomaestro B,Rotschafer J C,et al.Therapeutic monitoring of vancomycin in adult patients:A consensus review of the American society of health-system pharmacists,the infectious diseases society of America,and the society of infectious diseases pharmacists[J].Am JHealth Syst Pharm,2009,66(1):82-98.
[14]Ye Z K,Chen Y L,Chen K,et al.Therapeutic drug monitoring of vancomycin:A guideline of the division of therapeutic drug monitoring,Chinese Pharmacological Society[J].J Antimicrob Chemother,2016,71(11):3020-3025.
[15]Gordon C L,Thompson C,Carapetis J R,et al.Trough concentrations of vancomycin:adult therapeutic targets are not appropriate for children[J].Pediatr Infect Dis J,2012,31(12):1269-1271.
[16]Le J,Bradley J S,Murray W,et al.Improved vancomycin dosing in children using area under the curve exposure[J].Pediatr Infect Dis J,2013,32(4):155-163.
[17]叶志康,陈恳,Pleasants R A,等.万古霉素血药谷浓度和临床结局相关性的系统评价和Meta分析[J].药物流行病学杂志,2016,25(4):197-208.