title: CYP2C9 3 and 13 alleles significantly affect the pharmacokinetics of irbesartan in healthy Korean subjects.
abstract: OBJECTIVE
  To evaluate the effects of two major polymorphisms of CYP2C9, CYP2C9 3 and CYP2C9 13, on the pharmacokinetics of irbesartan in healthy Korean volunteers.
  
  
  METHODS
  A single 150-mg oral dose of irbesartan was given to 28 Korean volunteers, who had different CYP2C9 genotypes (12, 10, and 6 carriers of CYP2C9 1/ 1, 1/ 3, and 1/13 genotypes respectively). Irbesartan levels were analyzed using HPLC fluorescence in plasma samples collected up to 36 h after the drug intake.
  
  
  RESULTS
  Compared with CYP2C9 1 homozygous subjects, not only were the maximum plasma concentrations (C(max)) of irbesartan in CYP2C9 1/ 3 and 1/ 13 subjects 1.56- and 1.50-fold higher (P = 0.001), but the half-lives were also 1.38- and 1.50-fold longer (P = 0.001). The area under the plasma concentration-time curve (AUC) was 1.64- and 1.79-fold higher (P < 0.001). The oral clearance of irbesartan was 39.3% and 44.0% lower in the CYP2C9 1/ 3 and 1/ 13 subjects respectively, than in the 1/ 1 subjects (P < 0.001). Likewise, the increases in half-life and decreases in oral clearance observed in CYP2C9 1/ 13 individuals were similar to those in participants expressing the CYP2C9 1/ 3 genotype.
  
  
  CONCLUSIONS
  CYP2C9 genetic polymorphisms markedly affected the pharmacokinetics of irbesartan in this study sample. The CYP2C9 3 and CYP2C9 13 alleles appear to be associated with the decreased metabolism of irbesartan.
authors.affiliation: Laboratory of Pharmacology, School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Chang-Ik
authors.initials: CI
authors.lastname: Choi
authors.forename: Mi-Jeong
authors.initials: MJ
authors.lastname: Kim
authors.forename: Eun-Kyung
authors.initials: EK
authors.lastname: Chung
authors.forename: Hye-In
authors.initials: HI
authors.lastname: Lee
authors.forename: Choon-Gon
authors.initials: CG
authors.lastname: Jang
authors.forename: Jung-Woo
authors.initials: JW
authors.lastname: Bae
authors.forename: Seok-Yong
authors.initials: SY
authors.lastname: Lee
mesh_terms: D000483:Alleles; D047228:Angiotensin II Type 1 Receptor Blockers / Q000097:blood / Q000493:pharmacokinetics*; D000959:Antihypertensive Agents / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D001713:Biphenyl Compounds / Q000097:blood / Q000493:pharmacokinetics*; D065729:Cytochrome P-450 CYP2C9; D005838:Genotype; D006207:Half-Life; D006801:Humans; D000077405:Irbesartan; D011110:Polymorphism, Genetic; D013777:Tetrazoles / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D013777:Tetrazoles; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; D000077405:Irbesartan