Anti-inflammatory activity and pharmacokinetic profile of a new parenteral formulation of nimesulide.

Nimesulide, a selective COX-2 inhibitor, exerts potent anti-inflammatory and analgesic effects when administered orally, rectally or topically. The present study was designed to evaluate the anti-inflammatory activity of a new parenteral formulation of nimesulide and to correlate it with the pharmacokinetic profile. Nimesulide was administered intramuscularly at increasing doses of 1. 5, 3, 6, 12.5 and 25 mg kg-1 which produced dose-dependent anti-inflammatory effects in the carrageenan-induced rat paw edema. The anti-inflammatory activity of nimesulide was greater than that of diclofenac which was administered at identical doses though the difference was not statistically significant. Peak anti-inflammatory effects with nimesulide were observed between 2 and 3 h post-treatment which correlates well with the tmax of 115 min. The plasma concentration of nimesulide at different time points was assayed using HPLC after administration at a dose of 25 mg kg-1. Peak plasma concentration (Cmax) was 23 microgram ml-1 while t1/2 was derived as 4.2 h. Area Under Curve (AUC(0-6 h)) was calculated as 83. 31 microgram ml-1 h-1. No toxicity or adverse effects were noted at the doses administered. The present study demonstrates that nimesulide administered intramuscularly may be superior to other routes of administration when fast onset of action is required with high plasma concentration.