LACK OF PHARMACOKINETIC INTERACTION OF MELOXICAM WITH METHOTREXATE INPATIENTS WITH RHEUMATOID-ARTHRITIS

Objective. To investigate the pharmacokinetic interaction of oral melo xicam with intravenous (iv) methotrexate (MTX) in patients with rheuma toid arthritis (RA). Methods. Thirteen patients with RA received MTX 1 5 mg iv in the absence of nonsteroidal antiinflammatory drugs (NSAID) and after one week in the presence of steady state levels of meloxicam . Plasma concentrations of MTX and meloxicam were determined using val idated high performance liquid chromatography methods. One patient did not complete the study. The interaction of meloxicam and MTX was exam ined by equivalence testing. The endpoints AUC(MTX), V-ssMTX, Cl-totMT X, and C-maxMTX were analyzed parametrically, whereas endpoints MRTMTX , Cl-totMTX, t(1/2MTX), and t(maxMTX) were analyzed nonparametrically. Results. The MTX plasma concentrations over time, with and without me loxicam, did not differ significantly. The point estimator for the rat io of log transformed data of the primary endpoint AUC(MTX) was 108%; the lower 95% confidence limit was 100% and the upper 95% confidence l imit was 117%. Clinical laboratory values and adverse events revealed no increased MTX toxicity during concomitant treatment with meloxicam, Conclusion. In this short term interaction study there was no statist ically significant effect of meloxicam on the pharmacokinetics of MTX. The combination of MTX and meloxicam did not lead to increased MTX to xicity.