BACKGROUND: A novel class of nitric oxide-releasing nonsteroidal anti-inflammatory drug (NO-NSAID) derivatives has recently been described which exert anti-inflammatory activities but produce significantly less gastrointestinal injury than the parent NSAID from which they are derived. The present studies were performed to determine if a nitroxybutylester derivative of naproxen was less ulcerogenic to the gastrointestinal tract than its parent NSAID, and if it exerted comparable analgesic and anti-inflammatory properties to the parent NSAID. METHODS: The two drugs were compared in an acute gastric injury model, an antral ulcer model and after twice-daily administration for 18 days (small intestinal damage model). Anti-inflammatory activity was examined in the carrageenan-induced paw oedema model, while analgesia was examined in the acetic acid-induced writhing model. The pharmacokinetic profiles of naproxen vs. NO-naproxen were compared by HPLC analysis. RESULTS: NO-naproxen was found to produce significantly less gastric damage despite inducing similar increases in plasma TNF alpha to naproxen. With chronic administration, small intestinal damage was markedly less with NO-naproxen than with the parent NSAID. However, NO-naproxen exerted superior analgesic and comparable anti-inflammatory effects to naproxen. NO-naproxen was not completely converted to naproxen, but the reduced plasma levels of the latter was not the underlying reason for reduced gastrointestinal toxicity of NO-naproxen. CONCLUSION: NO-naproxen represents a novel, gastrointestinal-sparing NSAID derivative with superior analgesic and comparable anti-inflammatory properties to naproxen.
BACKGROUND: A novel class of nitric oxide-releasing nonsteroidal anti-inflammatory drug (NO-NSAID) derivatives has recently been described which exert anti-inflammatory activities but produce significantly less gastrointestinal injury than the parent NSAID from which they are derived. The present studies were performed to determine if a nitroxybutylester derivative of naproxen was less ulcerogenic to the gastrointestinal tract than its parent NSAID, and if it exerted comparable analgesic and anti-inflammatory properties to the parent NSAID. METHODS: The two drugs were compared in an acute gastric injury model, an antral ulcer model and after twice-daily administration for 18 days (small intestinal damage model). Anti-inflammatory activity was examined in the carrageenan-induced paw oedema model, while analgesia was examined in the acetic acid-induced writhing model. The pharmacokinetic profiles of naproxen vs. NO-naproxen were compared by HPLC analysis. RESULTS:NO-naproxen was found to produce significantly less gastric damage despite inducing similar increases in plasma TNF alpha to naproxen. With chronic administration, small intestinal damage was markedly less with NO-naproxen than with the parent NSAID. However, NO-naproxen exerted superior analgesic and comparable anti-inflammatory effects to naproxen. NO-naproxen was not completely converted to naproxen, but the reduced plasma levels of the latter was not the underlying reason for reduced gastrointestinal toxicity of NO-naproxen. CONCLUSION:NO-naproxen represents a novel, gastrointestinal-sparing NSAID derivative with superior analgesic and comparable anti-inflammatory properties to naproxen.
Authors: Ilja Tachecí; Jaroslav Kvetina; Jan Bures; Jan Osterreicher; Martin Kunes; Jaroslav Pejchal; Stanislav Rejchrt; Stanislav Spelda; Marcela Kopácová Journal: Dig Dis Sci Date: 2009-12-16 Impact factor: 3.199
Authors: T Mahmud; S Somasundaram; G Sigthorsson; R J Simpson; S Rafi; R Foster; I A Tavares; A Roseth; A J Hutt; M Jacob; J Pacy; D L Scott; J M Wrigglesworth; I Bjarnason Journal: Gut Date: 1998-12 Impact factor: 23.059