Pharmacokinetics and pharmacodynamics of meloxicam in relation to CYP2C9 genotype

Purpose: Meloxicam is a nonsteroidal anti-inflammatory drugs (NSAIDs) that exhibits anti-inflammatory, analgesic and antipyretic effects via a selective inhibition of cyclooxygenase-2 (COX-2). Meloxicam is almost completely metabolized to four inactive metabolites, and CYP2C9 plays an important role in the conversion of meloxicam into 5’-hydroxymethyl metabolite. We investigated effects of different CYP2C9 genotypes on the pharmacokinetics and pharmacodynamics of meloxicam.

Methods: Twenty-one subjects were selected and they were divided into three different groups according to CYP2C9 genotype, CYP2C9EM (CYP2C9*1/*1, n=11), CYP2C9IM (CYP2C9*1/*3, n=8) and CYP2C9PM (CYP2C9*3/*3, n=2). After overnight fasting, each subject received a single oral dose of 15 mg meloxicam. Blood samples were collected up to 72 hr after drug intake, and plasma concentrations of meloxicam were determined by a validated HPLC-UV analytical method.

Results: AUC_inf of meloxicam in CYP2C9IM group was 1.7-fold higher than that in CYP2C9EM group (74.6 ± 16.1 μg·hr/mL vs. 42.8 ± 13.3 μg·hr/mL, P<0.001). Apparent oral clearance (CL/F) and elimination half-life (t_1/2) of meloxicam between CYP2C9EM and CYP2C9IM groups was also significantly different (P<0.01 and P<0.001, respectively). AUC_inf of meloxicam in CYP2C9PM group (341.8 ± 37.4 μg·hr/mL) was almost 8.0-fold higher compared with that in CYP2C9EM group. The rate of TXB₂ production was significantly lower in the CYP2C9IM and PM groups than in the CYP2C9EM group.

Conclusion: CYP2C9 genetic polymorphism seems to be associated with the pharmacokinetics and pharamcodynamics of meloxicam.