Hee-Doo Yoo1, Mi-Suk Kim, Hea-Young Cho, Yong-Bok Lee. 1. College of Pharmacy and Institute of Bioequivalence and Bridging Study, Chonnam National University, 300 Yongbong-Dong, Buk-Gu, Gwangju, 500-757, South Korea.
Abstract
PURPOSE: The purpose of this study was to develop a population pharmacokinetic (PPK) model of glimepiride and to investigate the influence of genetic polymorphisms in CYP2C9 on the PPK of glimepiride in healthy Korean subjects. METHODS: Serum data after a single oral dose of 2 mg of glimepiride in 177 healthy male Korean subjects (CYP2C9*1*1: 163 subjects, *1/*3: 14 subjects) were used. We estimated the PPK of glimepiride using a nonlinear mixed effects modeling (NONMEM) method and explored the possible influence of genetic polymorphisms in CYP2C9 on the PPK of glimepiride. RESULTS: The disposition of glimepiride was best described with a two-compartment model with a Weibull-type absorption and first-order elimination. The visual predictive check indicated that the pharmacokinetic profile of glimepiride was adequately described by the proposed PPK model. The CYP2C9 genotypes as covariate significantly (P < 0.001) influenced the apparent oral clearance (CL/F) of glimepiride. The estimated CL/F of glimepiride was higher (1.60-fold) in CYP2C9*1/*1 subjects than in CYP2C9*1/*3 subjects. CONCLUSIONS: This study indicates that genetic polymorphisms of CYP2C9 influence the substantial interindividual variability in the disposition of glimepiride, and these polymorphisms may affect the clinical response to glimepiride therapy.
RCT Entities:
PURPOSE: The purpose of this study was to develop a population pharmacokinetic (PPK) model of glimepiride and to investigate the influence of genetic polymorphisms in CYP2C9 on the PPK of glimepiride in healthy Korean subjects. METHODS: Serum data after a single oral dose of 2 mg of glimepiride in 177 healthy male Korean subjects (CYP2C9*1*1: 163 subjects, *1/*3: 14 subjects) were used. We estimated the PPK of glimepiride using a nonlinear mixed effects modeling (NONMEM) method and explored the possible influence of genetic polymorphisms in CYP2C9 on the PPK of glimepiride. RESULTS: The disposition of glimepiride was best described with a two-compartment model with a Weibull-type absorption and first-order elimination. The visual predictive check indicated that the pharmacokinetic profile of glimepiride was adequately described by the proposed PPK model. The CYP2C9 genotypes as covariate significantly (P < 0.001) influenced the apparent oral clearance (CL/F) of glimepiride. The estimated CL/F of glimepiride was higher (1.60-fold) in CYP2C9*1/*1 subjects than in CYP2C9*1/*3 subjects. CONCLUSIONS: This study indicates that genetic polymorphisms of CYP2C9 influence the substantial interindividual variability in the disposition of glimepiride, and these polymorphisms may affect the clinical response to glimepiride therapy.
Authors: Julia Kirchheiner; Ivar Roots; Mark Goldammer; Bernd Rosenkranz; Jürgen Brockmöller Journal: Clin Pharmacokinet Date: 2005 Impact factor: 6.447
Authors: S P Myrand; K Sekiguchi; M Z Man; X Lin; R-Y Tzeng; C-H Teng; B Hee; M Garrett; H Kikkawa; C-Y Lin; S M Eddy; J Dostalik; J Mount; J Azuma; Y Fujio; I-J Jang; S-G Shin; M R Bleavins; J A Williams; J D Paulauskis; K D Wilner Journal: Clin Pharmacol Ther Date: 2008-03-19 Impact factor: 6.875