PHARMACOKINETICS OF MELOXICAM IN PATIENTS WITH END-STAGE RENAL-FAILURE ON HEMODIALYSIS - A COMPARISON WITH HEALTHY-VOLUNTEERS

Objective: The pharmacokinetics of meloxicam have been studied followi ng administration of a single 15-mg capsule to 12 patients with end-st age renal failure. Pharmacokinetic parameters were determined after ha emodialysis. The pharmacokinetic profile obtained in these patients is compared to data obtained from age- and gender-matched healthy volunt eers. Results: Total plasma meloxicam concentrations were lower in pat ients with end-stage renal failure (AUC(0-infinity) 12.6 mu g . h . ml (-1)) in comparison with healthy volunteers (AUC(0-infinity) 39.3 mu g . h . ml(-1)). This was reflected by an increase in total clearance ( +211%). However, there was an enhanced free meloxicam fraction (unboun d drug) in the end-stage renal failure patients (0.9% vs. 0.3% in heal thy volunteers). This was observed in association with raised free C-m ax (5.0 vs. 2.6 ng/ml) but similar free AUC(0-infinity)(0.13 vs. 0.11 mu g . h . ml(-1)) in both groups. Therefore, the raised free fraction is compensated for by the increased total clearance such that no accu mulation of meloxicam occurs. Meloxicam plasma concentrations were sim ilar before and after haemodialysis. Conclusion: Meloxicam has display ed a pharmacokinetic profile in end-stage renal failure which is simil ar to that observed for other highly protein bound nonsteroidal anti-i nflammatory drugs (NSAIDs). However, in view of the higher free C-max value, and despite no evidence of accumulation, it may be prudent to t reat this group of patients with a 7.5-mg dose of meloxicam. This is t he lower dose normally recommended for adults. Meloxicam is not dialys able.