文章基本信息

标题：Nonlinear Mixed Effects Model Analysis of the Pharmacokinetics of Aripiprazole in Healthy Japanese Males
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作者：Toshiko Koue ; Masanori Kubo ; Tomoo Funaki 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2007
卷号：30
期号：11
页码：2154-2158
DOI：10.1248/bpb.30.2154
出版社：The Pharmaceutical Society of Japan
摘要：The population pharmacokinetic parameters of aripiprazole in healthy Japanese males were estimated using a nonlinear mixed effects model (NONMEM) program. Pharmacokinetic data for population analysis were obtained from the single-dose (24 subjects), multiple-dose (15 subjects), and itraconazole-coadministration (27 subjects) trials. The time course of plasma aripiprazole concentration following oral administration was well described by a two-compartment model with first-order input. The mean values of the absorption lag time ( ALAG ) and absorption rate constant ( KA ) were estimated to be 0.805 h and 2.65 h⁻¹, respectively. The mean volume of the central ( V ₁/ F ) and peripheral ( V ₂/ F ) compartment was 3.84 and 1.54 l/kg, respectively, and the mean value of inter-compartment clearance ( Q / F ) was 0.168 l/h/kg. Oral clearance ( CL / F ) was estimated to be 0.0645 l/h/kg in the group with CYP2D6 * 1 /* 1 , * 1 /* 2 and * 2 /* 2 . The decrease in CL / F was estimated to be 0.0135 l/h/kg in the group with CYP2D6 * 1 /* 5 , * 1 /* 10 , * 2 /* 5 , * 2 /* 10 , and * 2 /* 41 , and 0.0293 l/h/kg in the group with CYP2D6 * 5 /* 10 , * 10 /* 10 , and * 41 /* 41 . The plasma concentration of aripiprazole was increased by coadministration of itraconazole, and the decrease in CL / F was estimated to be 0.0181 l/h/kg.
关键词：aripiprazole;two-compartment model;itraconazole;CYP2D6 genotype;nonlinear mixed-effect model;pharmacokinetic