Anti-inflammatory activity and pharmacokinetic profile of a new parenteralformulation of nimesulide

Nimesulide, a selective COX-2 inhibitor, exerts potent anti-inflammatory an d analgesic effects when administered orally, rectally or topically. The pr esent study was designed to evaluate the anti-inflammatory activity of a ne w parenteral formulation of nimesulide and to correlate it with the pharmac okinetic profile. Nimesulide was administered intramuscularly at increasing doses of 1.5, 3, 6, 12.5 and 25 mg kg(-1) which produced dose-dependent an ti-inflammatory effects in the carrageenan-induced rat paw edema. The anti- inflammatory activity of nimesulide was greater than that of diclofenac whi ch was administered at identical doses though the difference was not statis tically significant. Peak anti-inflammatory effects with nimesulide were ob served between 2 and 3 h post-treatment which correlates well with the t(ma x) of 115 min. The plasma concentration of nimesulide at different time poi nts was assayed using HPLC after administration at a dose of 25 mg kg(-1). Peak plasma concentration (C-max) was 23 mu g ml(-1) while t(1/2) was deriv ed as 4.2 h. Area Under Curve (AUC((0-6 h))) was calculated as 83.31 mu g m l(-1) h(-1). No toxicity or adverse effects were noted at the doses adminis tered. The present study demonstrates that nimesulide administered intramus cularly may be superior to other routes of administration when fast onset o f action is required with high plasma concentration. (C) 1999 The Italian P harmacological Society.