Population pharmacokinetic analysis of glimepiride with CYP2C9 genetic polymorphism in healthy Korean subjects

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