Anti-inflammatory activity of orpanoxin administered orally and topically to rodents.
Orpanoxin, a nonsteroidal anti-inflammatory drug (NSAID) lacking gastric ulcerogenic effects in the therapeutic dose range in rats, was compared with six reference NSAIDs for oral activity in the rat paw carrageenin-induced edema assay. Tested NSAIDs were ranked on the basis of oral mg/kg ED50 values: piroxicam, 0.55; orpanoxin, 35.6; diflunisal, 59.6; benoxaprofen, greater than 300; tolmetin sodium, greater than 300; and sulindac, greater than 300. Zomepirac sodium was inactive. Only the three most potent compounds produced greater than 60% inhibition of edema. Inhibition was generally greater at 4 h than at 6 h post carrageenin for all compounds. Oral activity of orpanoxin was also demonstrated in the guinea-pig u.v.-induced erythema model (ED50 = 24.2 mg/kg p.o. when given 1 h before irradiation) and in the mouse ear croton oil induced edema test (ED50 value = 131 mg/kg p.o.). Topical activity of orpanoxin was assessed in both the guinea-pig and mouse models. In the guinea-pig u.v.-induced erythema model, application (1 h after u.v.) of 1, 5, and 10% (w/v) orpanoxin creams (containing 10% urea) significantly inhibited erythema at 2, 3, and 4 h post-irradiation. Orpanoxin, mefenamic acid, and indomethacin as 1% creams inhibited total erythema scores 70, 92 and 74%, respectively. Evidence for topical activity in the mouse ear assay was also obtained for orpanoxin in diethyl ether or 10% urea cream, but not in dimethylsulfoxide. It was concluded that orpanoxin has anti-inflammatory activity comparable to reference NSAIDs in the rat paw edema test, is active orally in rat, mouse, and guinea-pig models, and shows topical activity in the guinea-pig and the mouse.
D000284:Administration, Oral; D000287:Administration, Topical; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D002351:Carrageenan; D003436:Croton Oil; D004061:Diflunisal / Q000627:therapeutic use; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D004890:Erythema / Q000188:drug therapy / Q000209:etiology; D006168:Guinea Pigs; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy*; D008297:Male; D051379:Mice; D010894:Piroxicam; D011422:Propionates / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains; D013843:Thiazines / Q000627:therapeutic use; D014466:Ultraviolet Rays
D000893:Anti-Inflammatory Agents; D011422:Propionates; D013843:Thiazines; D010894:Piroxicam; D004061:Diflunisal; D003436:Croton Oil; D002351:Carrageenan; C024876:orpanoxin