title: Strongly increased exposure of meloxicam in CYP2C9*3/*3 individuals.
abstract: OBJECTIVE
  The effects of CYP2C9*1/*3 and *3/*3 genotypes on the pharmacokinetics and pharmacodynamics of meloxicam were evaluated in healthy Korean subjects.
  
  
  METHODS
  After oral administration of 15 mg meloxicam, the plasma concentrations of meloxicam were assessed in 11 CYP2C9*1/*1 individuals, eight CYP2C9*1/*3 individuals, and three CYP2C9*3/*3 individuals. The pharmacodynamic effects were determined by measuring thromboxane B2 generated in blood.
  
  
  RESULTS
  A nine-fold lower apparent oral clearance and an eight-fold higher AUC0-∞ of single-dose meloxicam were observed in CYP2C9*3/*3 individuals when compared with CYP2C9*1/*1 individuals. CYP2C9*3/*3 individuals also showed markedly increased inhibition of thromboxane B2 generation by meloxicam.
  
  
  CONCLUSIONS
  These results indicate that CYP2C9*3/*3 individuals may be at a higher risk for concentration-dependent adverse effects during long-term treatment with standard doses of meloxicam.
authors: aDepartment of Pharmacology, School of Pharmacy, Sungkyunkwan University, Suwon bDepartment of Pharmacology, College of Pharmacy, Keimyung University, Daegu cDepartment of Pharmacotherapy, College of Pharmacy, Dankook University, Cheonan, Republic of Korea.
authors: Hye-In
authors: HI
authors: Lee
authors: Jung-Woo
authors: JW
authors: Bae
authors: Chang-Ik
authors: CI
authors: Choi
authors: Yun-Jeong
authors: YJ
authors: Lee
authors: Ji-Yeong
authors: JY
authors: Byeon
authors: Choon-Gon
authors: CG
authors: Jang
authors: Seok-Yong
authors: SY
authors: Lee
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D044466:Asian People; D065729:Cytochrome P-450 CYP2C9; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D000077239:Meloxicam; D008657:Metabolic Clearance Rate / Q000235:genetics; D011110:Polymorphism, Genetic; D013843:Thiazines / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D013844:Thiazoles / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D013929:Thromboxane B2 / Q000097:blood*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D013843:Thiazines; D013844:Thiazoles; D013929:Thromboxane B2; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; D000077239:Meloxicam