Effects of CYP2C9*1/*13 on the pharmacokinetics and pharmacodynamics of meloxicam

Abstract

To determine the effects of the CYP2C9*1/*13 genotype on the pharmacokinetics and pharmacodynamics of meloxicam in Korean subjects. METHODS Meloxicam (15mg) was orally administered to 21 healthy Korean volunteers with either the CYP2C9*1/*1 or the CYP2C9*1/*13 genotype. Plasma meloxicam concentrations were analysed by HPLC-UV for 72h after drug administration. The pharmacodynamic effects of meloxicam were determined by measuring TXB2 generated in blood. RESULTS The AUC(0,∞) and Cmax of meloxicam were 2.43- and 1.46-fold higher in the CYP2C9*1/*13 group than in the CYP2C9*1/*1 group, respectively. The oral clearance of meloxicam was significantly lower in the CYP2C9*1/*13 group (37.9% of wild type) than in the CYP2C9*1/*1 group. The t1/2 of meloxicam was 1.84-fold longer in the CYP2C9*1/*13 group than in the CYP2C9*1/*1 group. The rate of TXB2 production was significantly lower in the CYP2C9*1/*13 group than in the CYP2C9*1/*1 group. CONCLUSIONS The CYP2C9*1/*13 genotype is associated with decreased metabolism and increased pharmacodynamic effects of meloxicam. © 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society.