Shah I A, Whiting P H, Omar G, Ormerod A D, Burke M D
Department of Clinical Biochemistry, University of Aberdeen, U.K.
Br J Dermatol. 1993 Oct;129(4):395-8. doi: 10.1111/j.1365-2133.1993.tb03164.x.
Following the observation of increased trough whole blood cyclosporin A (CyA) concentrations and reduced renal function in a patient with recalcitrant generalized pustular psoriasis treated with a combination of CyA and etretinate, the effect of vitamin A analogues on human microsomal cytochrome P450-dependent CyA metabolism was investigated in vitro. In addition, the effect of terbinafine, a new allylamine antifungal agent, was also tested. Etretinate, its major metabolite acitretin, and isotretinoin, each at a single concentration of 100 microM, inhibited total hepatic microsomal CyA metabolism to a similar extent (33-45%, compared with control values). The generation of total primary and total secondary CyA metabolites was also inhibited to a similar extent by each of the retinoids. Conversely, terbinafine was without significant effect on CyA metabolism in vitro. The results, which suggest that inhibition of hepatic CyA metabolism by retinoids may contribute to increased circulating CyA concentrations, are discussed in relation to other potential drug interactions, and to the use of etretinate in reducing the CyA administered dose.
在观察到一名顽固性泛发性脓疱型银屑病患者联合使用环孢素A（CyA）和阿维A治疗后谷值全血环孢素A浓度升高且肾功能减退后，体外研究了维生素A类似物对人微粒体细胞色素P450依赖性环孢素A代谢的影响。此外，还测试了新型烯丙胺类抗真菌药特比萘芬的作用。阿维A、其主要代谢产物阿维A酸和异维A酸，各自在100微摩尔的单一浓度下，对肝微粒体中环孢素A的总代谢抑制程度相似（与对照值相比为33% - 45%）。每种维甲酸对环孢素A总初级代谢产物和总次级代谢产物的生成抑制程度也相似。相反，特比萘芬在体外对环孢素A代谢无显著影响。这些结果提示维甲酸对肝中环孢素A代谢的抑制可能导致循环中环孢素A浓度升高，本文结合其他潜在药物相互作用以及阿维A在降低环孢素A给药剂量方面的应用对这些结果进行了讨论。
