Effects of CYP2C9 genetic polymorphisms on the pharmacokinetics of celecoxib and its carboxylic acid metabolite

• Published in: Archives of pharmacal research 2017, 40(3), , pp.382-390
• Main Authors: Kim, Se-Hyung, Kim, Do-Hoon, Byeon, Ji-Yeong, Kim, Young-Hoon, Kim, Dong-Hyun, Lim, Hye-Jin, Lee, Choong-Min, Whang, Sang Sup, Choi, Chang-Ik, Bae, Jung-Woo, Lee, Yun Jeong, Jang, Choon-Gon, Lee, Seok-Yong
• Format: Article
• Language: English
• Subjects: Alleles; Asian Continental Ancestry Group - genetics; Carboxylic Acids - metabolism; Celecoxib - pharmacokinetics; Cyclooxygenase 2 Inhibitors - pharmacokinetics; Cytochrome P-450 CYP2C9 - genetics; Cytochrome P-450 CYP2C9 - metabolism; Female; Genetic Variation; Genotype; Humans; Male; Medicine; Pharmacology/Toxicology; Pharmacy; Polymorphism, Genetic; Research Article; Young Adult; 약학
• ISSN: 0253-6269; 1976-3786
• DOI: 10.1007/s12272-016-0861-2

Celecoxib, a selective cyclooxygenase (COX)-2 inhibitor, is used for the treatment of rheumatoid arthritis and osteoarthritis. The predominant hepatic metabolism of celecoxib to celecoxib carboxylic acid (CCA) is mediated mainly by CYP2C9. We investigated the effects of the major CYP2C9 genetic variants in Asian populations, CYP2C9*3 and CYP2C9*13 , on the pharmacokinetics of celecoxib and its carboxylic acid metabolite in healthy Korean subjects. A single 200-mg oral dose of celecoxib was given to 52 Korean subjects with different CYP2C9 genotypes: CYP2C9EM (n = 26; CYP2C9*1/*1 ), CYP2C9IM (n = 24; CYP2C9*1/*3 and *1/*13 ), and CYP2C9PM (n = 2; CYP2C9*3/*3 ). Celecoxib and CCA concentrations in plasma samples collected up to 48 or 96 h after drug intake were determined by HPLC–MS/MS. The mean area under the plasma concentration–time curve (AUC 0–∞ ) of celecoxib was increased 1.63-fold ( P