Combined Inhibition Effects of Tacrolimus and Methylprednisolone on in Vitro Human Lymphocyte Proliferation

Tacrolimus (FK 506) has synergistic immunosuppressive effects in combination with corticosteroids. A steroid dose-lowering effect can be explained partly by the inhibition by FK 506 of cytochrome P-450 IIIA, which metabolizes corticosteroids. We investigated the influence of combinations of FK 506 and methylprednisolone (MPL) on the suppression of in vitro human lymphocyte proliferation. To quantify the type of drug interaction (synergistic, additive, and antagonistic), three methods (Drewinko's statistical analysis, median-effect principle, and normal distribution model) were used. The interaction appeared synergistic in most combination ratios, but the extent of synergism varied depending on the quantitative method. There may be optimal combination ratios of FK 506 and MPL which achieve more effective immunosuppressive effects.