title: Population pharmacokinetic analysis of glimepiride with CYP2C9 genetic polymorphism in healthy Korean subjects.
abstract: OBJECTIVE
  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.affiliation: College of Pharmacy and Institute of Bioequivalence and Bridging Study, Chonnam National University, 300 Yongbong-Dong, Buk-Gu, Gwangju, 500-757, South Korea.
authors.forename: Hee-Doo
authors.initials: HD
authors.lastname: Yoo
authors.forename: Mi-Suk
authors.initials: MS
authors.lastname: Kim
authors.forename: Hea-Young
authors.initials: HY
authors.lastname: Cho
authors.forename: Yong-Bok
authors.initials: YB
authors.lastname: Lee
mesh_terms: D000042:Absorption; D000284:Administration, Oral; D000328:Adult; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D018592:Cross-Over Studies; D065729:Cytochrome P-450 CYP2C9; D006801:Humans; D007004:Hypoglycemic Agents / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008657:Metabolic Clearance Rate; D008954:Models, Biological; D009061:Mouth Mucosa / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D056910:Republic of Korea; D013453:Sulfonylurea Compounds / Q000097:blood / Q000493:pharmacokinetics*; D013810:Therapeutic Equivalency; D055815:Young Adult
chemical_list: D007004:Hypoglycemic Agents; D013453:Sulfonylurea Compounds; C057619:glimepiride; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases