Effects of CYP2C9 genetic polymorphisms on the pharmacokinetics of zafirlukast

• Published in: Archives of pharmacal research 2016, 39(7), , pp.1013-1019
• Main Authors: Lee, Hyun-Jee, Kim, Young-Hoon, Kim, Se-Hyung, Lee, Choong-Min, Yang, Ae-Yun, Jang, Choon-Gon, Lee, Seok-Yong, Bae, Jung-Woo, Choi, Chang-Ik
• Format: Article
• Language: English
• Subjects: Administration, Oral; Adult; Anti-Asthmatic Agents - administration & dosage; Anti-Asthmatic Agents - pharmacokinetics; Asian Continental Ancestry Group - genetics; Cytochrome P-450 CYP2C9 - genetics; Cytochrome P-450 CYP2C9 - metabolism; Humans; Male; Medicine; Pharmacology/Toxicology; Pharmacy; Polymorphism, Genetic - drug effects; Polymorphism, Genetic - genetics; Research Article; Tosyl Compounds - administration & dosage; Tosyl Compounds - pharmacokinetics; Young Adult; 약학
• ISSN: 0253-6269; 1976-3786
• DOI: 10.1007/s12272-016-0785-x

Zafirlukast, a cysteinyl leukotriene receptor antagonist, is indicated for the treatment of patients with mild to moderate asthma. Zafirlukast is metabolized mainly by CYP3A4 and CYP2C9. We investigated the effects of the major CYP2C9 variant alleles in Asian populations, CYP2C9*3 and CYP2C9*13 , on the pharmacokinetics of zafirlukast in healthy Korean subjects. A single 20-mg oral dose of zafirlukast was given to 23 Korean male subjects divided into two genotype groups according to CYP2C9 genotypes, CYP2C9EM (n = 11; CYP2C9*1/*1 ) and CYP2C9IM (n = 12; 9 and 3 carriers of CYP2C9*1/*3 and *1/*13 , respectively). Zafirlukast concentrations were determined using a validated HPLC–MS/MS analytical method in plasma samples collected after the drug intake. Compared with the CYP2C9EM group, the C max and AUC inf of zafirlukast in the CYP2C9IM group were 1.44- and 1.70-fold higher, respectively (p