Abstract
Interactions of Y-8004 with anti-inflammatory agents were examined in the carrageenin foot edema and adjuvant induced arthritis tests. The combined administration of hydrocortisone with Y-8004 or other acidic non-steroidal anti-inflammatory agents resulted in a synergistic inhibition of edema. The therapeutic effect of a combination of hydrocortisone and Y-8004 was found to be greater than the effect produced by each of the component agents at corresponding doses in the adjuvant induced arthritis test. Y-8004 also maintained the therapeutic effect of prednisolone by alternative administration in succession to prednisolone therapy as well as indomethacin. On the other hand, the combined effect of acetylsalicylic acid with Y-8004 was antagonistic at the combined ratio in 25 to 1, but synergistic at the combined ratio in 100 to 1. Similar results were obtained in combinations of Y-8004 and indomethacin. The acute toxicity of Y-8004 in rats was potentiated by the combined administration of hydrocortisone or acetylsalicylic acid. The toxicity of indomethacin was, however, antagonized by a combined administration with acetylsalicylic acid as well as the anti-inflammatory activity of indomethacin. These results suggest that Y-8004 may make feasible a reduction in dosage or a withdrawal of the steroid prescription. Antagonism between non-steroidal antiinflammatory agents has yet to be established.
