Population pharmacokinetic analysis of glimepiride with CYP2C9 genetic polymorphism in healthy Korean subjects.
Eur J Clin Pharmacol
; 67(9): 889-98, 2011 Sep.
Article
em En
| MEDLINE
| ID: mdl-21476064
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Compostos de Sulfonilureia
/
Polimorfismo de Fragmento de Restrição
/
Hidrocarboneto de Aril Hidroxilases
/
Hipoglicemiantes
/
Modelos Biológicos
Tipo de estudo:
Clinical_trials
/
Prognostic_studies
Limite:
Adult
/
Humans
/
Male
País/Região como assunto:
Asia
Idioma:
En
Revista:
Eur J Clin Pharmacol
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Coréia do Sul