Abstract
The effects of CYP2C9*1/*3 and *3/*3 genotypes on the pharmacokinetics and pharmacodynamics of meloxicam were evaluated in healthy Korean subjects. After oral administration of 15 mg meloxicam, the plasma concentrations of meloxicam were assessed in 11 CYP2C9*1/*1 individuals, eight CYP2C9*1/*3 individuals, and three CYP2C9*3/*3 individuals. The pharmacodynamic effects were determined by measuring thromboxane B2 generated in blood. A nine-fold lower apparent oral clearance and an eight-fold higher AUC0-∞ of single-dose meloxicam were observed in CYP2C9*3/*3 individuals when compared with CYP2C9*1/*1 individuals. CYP2C9*3/*3 individuals also showed markedly increased inhibition of thromboxane B2 generation by meloxicam. These results indicate that CYP2C9*3/*3 individuals may be at a higher risk for concentration-dependent adverse effects during long-term treatment with standard doses of meloxicam.
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