Article date: April 2011
By: Jung‐Woo Bae, Chang‐Ik Choi, Choon‐Gon Jang, Seok‐Yong Lee, in Volume 71, Issue 4, pages 550-555
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 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.
DOI: 10.1111/j.1365-2125.2010.03853.x
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