Comparative anti-nociceptive, anti-inflammatory and toxicity profile of nimesulide vs nimesulide and piperine combination

Piperine is an inhibitor of various hepatic and other enzymes involved in t he biotransformation of drugs. Preliminary pharmacokinetic studies conducte d by us suggested the increased bioavailability of nimesulide co-administer ed with piperine. The present study was, thus, conducted to evaluate the an tinociceptive, anti-inflammatory and toxicity profile of a new nimesulide-p iperine combination administered orally as compared with nimesulide alone. Antinociceptive efficacy was tested using an acetic acid writhing test and tail flick latency test (TFL). The ED50 value of a nimesulide-piperine comb ination in writhing test was calculated to be significantly lower (1.5 mg k g(-1)) as compared to (11.2 mg kg(-1)) of nimesulide alone. The antinocicep tive effect was lesser in the tail flick latency test as compared to what w as observed in the writhing test indicating the peripheral action of the No n-Steriodal Anti-Inflammatory Drug (NSAID). In carrageenan-induced inflamma tory tests, the nimesulide-piperine combination was found to be dose-to-dos e superior than nimesulide alone. Acute toxicity studies on mice revealed a reduction in lethal dose (LD50) of the combination (980 mg kg(-1)) as comp ared to nimesulide (1500 mg kg(-1)) alone. Results from the present study s uggest a better therapeutic index for the nimesulide-piperine combination i ndicating that this combination would further reduce the frequency of adver se effects associated with nimesulide alone. (C) 2000 Academic Press.