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.