Effects of CYP2C9 genetic polymorphisms on the pharmacokinetics of zafirlukast.

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Lee HJ, Kim YH, Kim SH, Lee CM, Yang AY, Jang CG, Lee SY, Bae JW, Choi CI

Effects of CYP2C9 genetic polymorphisms on the pharmacokinetics of zafirlukast.

Arch Pharm Res. 2016 Jul;39(7):1013-9. doi: 10.1007/s12272-016-0785-x. Epub 2016 Jul 4.

PubMed ID

27377818 [ View in PubMed

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Abstract

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 Cmax and AUCinf of zafirlukast in the CYP2C9IM group were 1.44- and 1.70-fold higher, respectively (p < 0.01 and p < 0.0001). The CL/F of zafirlukast was 42.8 % lower in the CYP2C9IM group compared with the CYP2C9EM group (p < 0.001). Slightly higher Cmax and AUC, and lower CL/F of zafirlukast were observed in subjects with the CYP2C9*1/*13 genotype compared with the CYP2C9*1/*3 genotype subjects. CYP2C9*3 and CYP2C9*13 alleles significantly affected the plasma concentrations of zafirlukast.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Zafirlukast	Cytochrome P450 2C9	Protein	Humans	Unknown	Substrate Inhibitor	Details