title: Comparative anti-nociceptive, anti-inflammatory and toxicity profile of nimesulide vs nimesulide and piperine combination.
abstract: Piperine is an inhibitor of various hepatic and other enzymes involved in the biotransformation of drugs. Preliminary pharmacokinetic studies conducted by us suggested the increased bioavailability of nimesulide co-administered with piperine. The present study was, thus, conducted to evaluate the antinociceptive, anti-inflammatory and toxicity profile of a new nimesulide-piperine 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 combination in writhing test was calculated to be significantly lower (1.5 mg kg(-1)) as compared to (11.2 mg kg(-1)) of nimesulide alone. The antinociceptive effect was lesser in the tail flick latency test as compared to what was observed in the writhing test indicating the peripheral action of the Non-Steriodal Anti-Inflammatory Drug (NSAID). In carrageenan-induced inflammatory tests, the nimesulide-piperine combination was found to be dose-to-dose superior than nimesulide alone. Acute toxicity studies on mice revealed a reduction in lethal dose (LD50) of the combination (980 mg kg(-1)) as compared to nimesulide (1500 mg kg(-1)) alone. Results from the present study suggest a better therapeutic index for the nimesulide-piperine combination indicating that this combination would further reduce the frequency of adverse effects associated with nimesulide alone.
authors.affiliation: Department of Pharmacology, All India Institute of Medical Sciences, New Delhi, 110029, India.
authors.forename: S K
authors.initials: SK
authors.lastname: Gupta
authors.forename: P
authors.initials: P
authors.lastname: Bansal
authors.forename: R K
authors.initials: RK
authors.lastname: Bhardwaj
authors.forename: T
authors.initials: T
authors.lastname: Velpandian
mesh_terms: D000284:Administration, Oral; D000470:Alkaloids; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000633:toxicity; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000633:toxicity; D052117:Benzodioxoles; D004338:Drug Combinations; D004347:Drug Interactions; D005260:Female; D007249:Inflammation / Q000188:drug therapy*; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D009619:Nociceptors / Q000187:drug effects*; D010880:Piperidines / Q000008:administration & dosage* / Q000633:toxicity; D053284:Polyunsaturated Alkamides; D051381:Rats; D017208:Rats, Wistar; D013449:Sulfonamides / Q000008:administration & dosage* / Q000633:toxicity
chemical_list: D000470:Alkaloids; D018712:Analgesics, Non-Narcotic; D000894:Anti-Inflammatory Agents, Non-Steroidal; D052117:Benzodioxoles; D004338:Drug Combinations; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D013449:Sulfonamides; C008922:piperine; C012655:nimesulide