Gastrointestinal effects and acute toxicity of suprofen.
The acute effects of orally administered, high doses of alpha-methyl-4-(2-thienylcarbonyl)benzeneacetic acid (suprofen) were studied in various tests, related to gastrointestinal functions. A decrease of the diarrheal stools in the castor oil test in rats was the first effect noted; the ED50 in this test was 40 mg/kg. This dose is 540 times higher than the ED50 of suprofen in the acetic acid-induced writhing test in rats (ED50 = 0.074 mg/kg). Temporarily decreased food consumption in rats was first noted after administration of 80 mg/kg. This is more than 1000 times the ED50 in the rat anti-writhing test. The appearance of gastrointestinal lesions was also studied in rats and a direct quantitative comparison was made with indometacin, acetyl-salicylic acid and ketoprofen. The dose of suprofen that produced lesions in 50% of the rats was 200 mg/kg, viz. 2700 times the ED50 in the rat anti-writhing test. Similarly obtained safety margins are 9.0 for indometacin, 78 for acetyl-salicylic acid and 102 for ketoprofen. The mortality after a single oral administration of suprofen was studied in mice, rats, guinea-pigs and dogs. LD50-values, based on mortality 7 days after administration, were 590 mg/kg, 353 mg/kg, 280 mg/kg and more than 160 mg/kg, respectively. Comparative LD50's in mice and rats were 14 and 19 mg/kg for indometacin, 280 and 70 mg/kg for ketoprofen. Therefore the safety margin in rats, with respect to the ED50 in the acetic acid-induced writhing test, is 4770 for suprofen, 156 for ketoprofen and 17.3 for indometacin. In guinea-pigs the safety margin of suprofen is 1470 with respect to the ED50 in UV-erythema and in dogs more than 250 with respect to the ED50 in urate-induced arthritis. From these data we may conclude that suprofen is comparatively safer than the reference compounds studied and that its effects on the gastrointestinal tract appear at doses far above those required for effectiveness in tests related to pain, fever and inflammation.
D000818:Animals; D000930:Antidiarrheals; D001241:Aspirin / Q000633:toxicity; D004064:Digestive System / Q000187:drug effects*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004435:Eating / Q000187:drug effects; D005260:Female; D006168:Guinea Pigs; D007213:Indomethacin / Q000633:toxicity; D007660:Ketoprofen / Q000633:toxicity; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D010648:Phenylacetates / Q000633:toxicity; D010666:Phenylpropionates / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013876:Thiophenes / Q000494:pharmacology* / Q000633:toxicity; D013997:Time Factors; D014456:Ulcer / Q000139:chemically induced
D000930:Antidiarrheals; D010648:Phenylacetates; D010666:Phenylpropionates; D013876:Thiophenes; D007660:Ketoprofen; D001241:Aspirin; D007213:Indomethacin