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

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Meloxicam is a substrate for the CYP2C9 and CYP3A4 enzymes. • We have previously reported that the frequency of the CYP2C9*1/*13 genotype in the Korean population is 1.1%. WHAT THIS STUDY ADDS • The CYP2C9*1/*13 genotype is associated with decreased metabolism and increased pharmacodynamic effects of meloxicam. • This is the first report that evaluates the in vivo effects of the CYP2C9*13 allele on the pharmacokinetics and pharmacodynamics of CYP2C9 substrates with a sufficient sample size. AIMS To determine the effects of the CYP2C9*1/*13 genotype on the pharmacokinetics and pharmacodynamics of meloxicam in Korean subjects. METHODS Meloxicam (15 mg) 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 72 h after drug administration. The pharmacodynamic effects of meloxicam were determined by measuring TXB 2 generated in blood. RESULTS The AUC(0,∞) and C max 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 t 1/2 of meloxicam was 1.84‐fold longer in the CYP2C9*1/*13 group than in the CYP2C9*1/*1 group. The rate of TXB 2 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.