Maruyama Y, Imayoshi T, Foto K, Kadobe Y
Nihon Yakurigaku Zasshi. 1977 Jan;73(1):113-22. doi: 10.1254/fpj.73.113.
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 anti-inflammatory agents has yet to be established.
在角叉菜胶致足肿胀和佐剂性关节炎试验中研究了Y - 8004与抗炎药的相互作用。氢化可的松与Y - 8004或其他酸性非甾体抗炎药联合给药可协同抑制肿胀。在佐剂性关节炎试验中，发现氢化可的松与Y - 8004联合使用的治疗效果大于相应剂量的各组分药物单独使用时产生的效果。Y - 8004在泼尼松龙治疗以及吲哚美辛治疗后交替给药时，还能维持泼尼松龙的治疗效果。另一方面，乙酰水杨酸与Y - 8004按25比1的联合比例时联合效应具有拮抗作用，但按100比1的联合比例时具有协同作用。Y - 8004与吲哚美辛联合使用也得到了类似结果。氢化可的松或乙酰水杨酸联合给药可增强Y - 8004对大鼠的急性毒性。然而，吲哚美辛与乙酰水杨酸联合给药可拮抗其毒性以及吲哚美辛的抗炎活性。这些结果表明，Y - 8004可能使减少类固醇药物的剂量或停药成为可能。非甾体抗炎药之间的拮抗作用尚未得到证实。
