title: The effects of suprofen in rats with Mycobacterium butyricum-induced arthritis.
abstract: The activity of alpha-methyl-4-(2-thienylcarbonyl)benzeneacetic acid (suprofen) was studied in rats with established Mycobacterium butyricum-induced arthritis. The arthritic response was evaluated by measuring the diameter changes of the hind paws and tibiotarsal joints, using a new apparatus. Treatment once daily by gavage during 14 days revealed activity at the dose of 1.25 mg/kg and above. The lowest ED50 was 6.2 mg/kg. In comparison with simultaneously studied reference compounds, this corresponded approximately to the activity of phenylbutazone. In the higher dose range, 10 to 40 mg/kg, the reduction of external arthritic symptoms was associated with marked reversal of multiple bone deformations. A treatment schedule with 4 administrations of 2.5 mg/kg/day was significantly more effective than a single daily administration of 10 mg/kg and comparable to that of 10 mg/kg once daily. Mixing of suprofen with the diet, to give the low daily dose of 1.28 mg/kg confirmed the high activity expected from the maintenance of a practically constant compound level in the treated rats. In a comparative study involving suprofen, acetyl-salicylic acid, indometacin, phenylbutazone and tolmetin, all administered over 14 days with the diet in a dose range up to toxic dose levels, dose-related anti-inflammatory and toxic effects were obtained. The potency order and ED50's of the compounds were: indometacin (0.31 mg/kg) greater than suprofen (1.48) greater than tolmetin (18.0) = phenylbutazone (18.2) greater than acetyl-salicylic acid (440). Suprofen had by far the largest safety margin (48), followed by phenylbutazone (20), tolmetin (16), indometacin (8) and acetyl-salicylic acid (2). In conclusion, three major symptoms of adjuvant arthritis: joint inflammation, impaired growth and bone erosion, were markedly reduced by different doses of suprofen, which revealed to be a safe compound when compared to several reference compounds.
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000503:physiopathology; D001241:Aspirin / Q000627:therapeutic use; D001699:Biometry; D001835:Body Weight; D001842:Bone and Bones / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004353:Drug Evaluation, Preclinical; D006242:Haptoglobins / Q000032:analysis; D006614:Hindlimb; D007213:Indomethacin / Q000627:therapeutic use; D010653:Phenylbutazone / Q000627:therapeutic use; D010666:Phenylpropionates / Q000627:therapeutic use*; D051381:Rats; D013640:Tarsal Joints / Q000503:physiopathology; D013876:Thiophenes / Q000627:therapeutic use*; D014046:Tolmetin / Q000627:therapeutic use
chemical_list: D000893:Anti-Inflammatory Agents; D006242:Haptoglobins; D010666:Phenylpropionates; D013876:Thiophenes; D014046:Tolmetin; D010653:Phenylbutazone; D001241:Aspirin; D007213:Indomethacin