Lee M J, Pyszczynski N, Jusko W J
Department of Pharmaceutics, State University of New York at Buffalo 14260, USA.
Immunopharmacol Immunotoxicol. 1995 May;17(2):335-45. doi: 10.3109/08923979509019755.
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.
他克莫司（FK 506）与皮质类固醇联合使用具有协同免疫抑制作用。FK 506对细胞色素P-450 IIIA的抑制作用可部分解释其降低类固醇剂量的效果，细胞色素P-450 IIIA可代谢皮质类固醇。我们研究了FK 506与甲泼尼龙（MPL）联合使用对体外人淋巴细胞增殖抑制的影响。为了量化药物相互作用的类型（协同、相加和拮抗），使用了三种方法（德鲁因科统计分析、中位效应原理和正态分布模型）。在大多数组合比例下，相互作用表现为协同，但协同程度因定量方法而异。FK 506和MPL可能存在最佳组合比例，可实现更有效的免疫抑制作用。
