头孢克洛在中国健康志愿者体内的群体药代动力学研究

中国临床药理学与治疗学 ›› 2012, Vol. 17 ›› Issue (6): 659-665.

头孢克洛在中国健康志愿者体内的群体药代动力学研究

黄继汉¹, 黄晓晖², 王鲲¹, 李俊², 郑青山¹

¹上海中医药大学药物临床研究中心,上海 201203;
²安徽医科大学药学院基础与临床药理学教研室,合肥 230032,安徽

收稿日期:2012-04-11 修回日期:2012-05-08 出版日期:2012-06-26 发布日期:2012-06-25
通讯作者: 郑青山,男,教授,博导,研究方向:定量药理学和生物统计学研究。Tel: 021-51323006 E-mail: zheng.zqs@gmail.com
作者简介:黄继汉,男,博士,研究方向:临床药理学和定量药理学。Tel: 021-51322420 E-mail: whhuangjh@163.com;黄晓晖,共同第一作者,男,副教授,硕士生导师,研究方向:定量药理学和临床药代动力学。Tel: 13855183138 E-mail: mathdrug@sina.com
基金资助:
国家科技支撑计划项目(2008BAI51B03);安徽省优秀青年科技基金(08040106813);上海市教委创新项目(10YZ61)

Population pharmacokinetics of cefaclor in healthy Chinese adult male volunteers

HUANG Ji-han¹, HUANG Xiao-hui², WANG Kun¹, LI Jun², ZHENG Qing-shan¹

¹Department of Pharmacometrics, Center for Drug Clinical Research, Shanghai University of Chinese Medicine, Shanghai 201203, China;
²Department of Basic and Clinical Pharmacology, School of Pharmacy, Anhui Medical University, Hefei 230032, Anhui, China

Received:2012-04-11 Revised:2012-05-08 Online:2012-06-26 Published:2012-06-25

摘要/Abstract

摘要： 目的: 建立头孢克洛口服给药在健康志愿者体内的群体药代动力学模型,探讨个体因素对代谢反应的影响。方法: 基于头孢克洛生物等效性试验数据,应用非线性混合效应模型的群体方法分析头孢克洛口服给药的生物等效性试验数据,估算相关药代动力学参数及变异。结果: 头孢克洛在健康志愿者中符合一级吸收的二室模型。药物表观清除率(CL)、中央分布容积(V2)、中央分布容积(V3)、吸收速率常数(K_A)的群体典型值分别为 0.219 L/min、35.9 L、598 L 和 0.042 min^-1。体重对清除率(CL)有显著影响。结论: 群体药代动力学最终模型可对个体药代参数做出精确的估计,体重对表观清除率有影响。

关键词: 头孢克洛, 健康志愿者, 群体药代动力学

Abstract: AIM: To develop a population pharmacokinetic model of cefaclor in healthy volunteers and evalute the effect of individual factors on the pharmacokinetics of cefaclor. METHODS: A nonlinear mixed-effect modeling was developed to analyze the data of cefaclor bioequivalence studies in healthy volunteers and calculate the related parameters and inter- and intra variabilties. RESULTS: two-compartment model with first order absorption was fitted to the cefaclor concentration data. The population value of CL, V2, V3, K_A were 0.219 L/min, 35.9 L, 598 L, 0.042 min^-1, respectively. CL was found to be significantly related to the covariate of weight. CONCLUSION: The population pharmacokinetic model can be used to provide accurate individual pharmacokinetic parameters. CL was significantly influenced by the covariate of weight, which showed that it is better to administer drug according to the per kilogram of body weight in clinical practice.

Key words: Amlodipine, Healthy Volunteers, Population Pharmacokinetics

中图分类号:

R969

黄继汉, 黄晓晖, 王鲲, 李俊, 郑青山. 头孢克洛在中国健康志愿者体内的群体药代动力学研究[J]. 中国临床药理学与治疗学, 2012, 17(6): 659-665.

HUANG Ji-han, HUANG Xiao-hui, WANG Kun, LI Jun, ZHENG Qing-shan. Population pharmacokinetics of cefaclor in healthy Chinese adult male volunteers[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2012, 17(6): 659-665.

参考文献

[1] Kammer RB. Cefaclor in management of streptococcal pharyngitis, otitis media, and skin infections[J]. Ann Otol Rhinol Laryngol Suppl, 1981, 90(3):79-81.
[2] ZeLuff B, Catchpole M, Lowe P, et al. Cefadroxil compared with cefaclor in the treatment of streptococcal pneumonia in adults[J]. Drugs, 1986, 32(3): 39-42.
[3] Dorow P. Safety and efficacy of cefixime versus cefaclor in respiratory tract infections[J]. J Chemother, 1989, 1(4):257-260.
[4] Sheiner LB, Beal SL. NONMEM users guide, part V[S]. University of California, San Francisco. 1998.
[5] Sheiner LB, Beal SL.Pharmacokinetic parameter estimates from several least squares procedures:superiority of extended least squares[J].J Pharmacokinet Biopharm, 1985,13(2):185-201.
[6] Sheiner LB. The population approach to pharmacokinetic data analysis: rationale and standard data analysis methods[J]. Drug Metabolism Reviews, 1984, 15(1):153-171.
[7] Mandema JW, Verotta D, Sheiner LB. Building population pharmacokinetic-pharmacodynamic models. I. Models for covariate effects[J]. J Pharmacokinet Biopharm, 1992,20:511-528.
[8] Ribbing J, Jonsson EN. Power, selection bias and predictive performance of the Population Pharmacokinetic Covariate Model[J]. J Pharmacokinet Pharmacodyn, 2004,31(2): 109-134.
[9] Ribbing J, Nyberg J, Caster O, et al.The lasso-a novel method for predictive covariate model building in nonlinear mixed effects models[J].J Pharmacokinet Pharmacodyn, 2007, 34(4): 485-517.
[10] Ribbing J, Hooker AC, Jonsson EN. Non-Bayesian knowledge propagation using model-based analysis of data from multiple clinical studies[J]. J Pharmacokinet Pharmacodyn, 2008, 35(1): 117-137.
[11] Ribbing J, Hamrén B, Svensson MK, et al.A model for glucose, insulin, and beta-cell dynamics in subjects with insulin resistance and patients with type 2 diabetes[J]. J Clin Pharmacol, 2010, 50(8):861-872.
[12] Efron B. Bootstrap methods: another Look at the Jackknife[J]. Ann Stat, 1979,7(1): 1-12.
[13] 盛玉成, 郑青山. 群体药代动力学及其在新药研究中的应用[J]. 中国临床药理学与治疗学, 2004, 9(12): 1333-1334.
[14] 黄晓晖,黄继汉, 李禄金, 等. 氨氯地平在中国健康志愿者体内的群体药动学研究[J]. 中国临床药理学与治疗学杂志, 2011,16(2): 1383-1390.

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