氨氯地平在中国健康志愿者体内的群体药动学研究

中国临床药理学与治疗学 ›› 2011, Vol. 16 ›› Issue (12): 1383-1390.

氨氯地平在中国健康志愿者体内的群体药动学研究

黄晓晖¹, 黄继汉², 李禄金², 王鲲², 杨娟², 郑青山²

¹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;
²上海中医药大学药物临床研究中心,上海 201203

收稿日期:2011-11-09 修回日期:2011-11-20 出版日期:2011-12-26 发布日期:2012-01-07

Population pharmacokinetics of amlodipine in healthy Chinese adult male volunteers

HUANG Xiao-hui¹, HUANG Ji-han², LI Lu-jin², WANG Kun², YANG Juan², ZHENG Qing-shan²

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

Received:2011-11-09 Revised:2011-11-20 Online:2011-12-26 Published:2012-01-07
Contact: Prof. Qingshan Zheng, Corresponding author, professor of pharmacometrics.Tel: 13817078595 E-mail: drugchina@126.com
About author:Xiaohui Huang and Jihan Huang contributed equally to this work.
Supported by:
This study was supported by the National Science and Technology Supporting Project of China (2008BAI51B03);the Leading Academic Discipline Project of Shanghai Municipal Education Commission (J50303) and Innovation Program of Shanghai Municipal Education Commission(10YZ61)

摘要/Abstract

摘要： 氨氯地平用以治疗高血压和心绞痛的药物,属于第三代双氢吡啶类钙通道阻滞剂。本研究对来自3个氨氯地平生物等效性试验的60个健康志愿者数据进行氨氯地平的群体药代动力学分析。数据及协变量用非线性混合效应模型NONMEN拟合分析。一级吸收的二室模型用以拟合氨氯地平血药浓度数据。在建模过程中没有找到显著的协变量。个体内(残余)变异用变异系数表示,为18.7%。CL, V₂,V₃和K_a的个体间变异分别为27.3%, 26.6%, 49.9% 和 65.7%。V₃和K_a的个体间变异相对较高(>40%),可能因为氨氯地平吸收和处置过程中的基因变异所导致。

关键词: 氨氯地平, 群体药代动力学, 非线性混合效应模型

Abstract: Amlodipine is a third-generation dihydropyridine calcium channel blocker that is indicated for treatment of hypertension and angina in adults. The population pharmacokinetics of amlodipine was evaluated in 60 healthy volunteers enrolled in three bioequivalence studies. These data, along with a set of covariates, were the subject of a nonlinear mixed-effect modeling analysis using the NONMEM program. A two-compartment model with first order absorption was fitted to the serum amlodipine concentration data. No significant covariates were found in the model-building. The intraindividual (residual) variability expressed as coefficient of variation was 18.7%, whereas the interindividual variability of CL, V₂,V₃ and K_a,was 27.3%, 26.6%, 49.9% and 65.7%, respectively. The relatively high (>40%) interindividual variability for V₃ and K_a parameters, observed under the controlled experimental settings of bioequivalence trials in healthy volunteers, may result from genetic variability of the processes involved in amlodipine absorption and disposition.

Key words: Amlodipine, Population Pharmacokinetics, NONMEM

中图分类号:

R969.1

黄晓晖, 黄继汉, 李禄金, 王鲲, 杨娟, 郑青山. 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, 2011, 16(12): 1383-1390.

HUANG Xiao-hui, HUANG Ji-han, LI Lu-jin, WANG Kun, YANG Juan, ZHENG Qing-shan. Population pharmacokinetics of amlodipine in healthy Chinese adult male volunteers[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2011, 16(12): 1383-1390.

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