Tillement J P, Albengres E
Service Hospitalo-Universitaire de Pharmacologie de l'Université de Paris XII, Faculté de Médecine, Créteil, France.
Therapie. 1995 May-Jun;50(3):185-9.
Cyclosporin A is potentiated by ketoconazole, mainly by inhibiting its P-450 dependent biotransformations. The other interest of ketoconazole is related to its antifungal effect, which is often used in immunodepressed patients. Thus for both pharmacodynamic and pharmacokinetic reasons, the combination of the two drugs is of interest. Another advantage is that whereas ketoconazole is a cheap drug, cyclosporin A is an expensive one, thus their combination may save a part of the cyclosporin A cost. Various questions remain to be solved: is it useful to combine in the same tablet selected amounts of the two drugs and if so in which ratio? Such a strategy supposes that intra and inter-individual variability of cyclosporin A metabolism in humans can be tightly monitored. Is it without risk to definitely inhibit some P-450 isoenzymes? Could not the expected simplification of drug dosages generate the need for more cyclosporin A blood level assays, thus leading to an additional cost?
酮康唑可增强环孢素A的作用，主要是通过抑制其依赖细胞色素P-450的生物转化。酮康唑的另一个优势与其抗真菌作用有关，它常用于免疫功能低下的患者。因此，基于药效学和药代动力学两方面的原因，这两种药物的联合使用具有重要意义。另一个优点是，酮康唑是一种廉价药物，而环孢素A价格昂贵，因此它们的联合使用可能会节省一部分环孢素A的费用。仍有各种问题有待解决：将选定剂量的两种药物制成同一片剂是否有用？如果有用，应以何种比例？这种策略假定可以严密监测人体中环孢素A代谢的个体内和个体间变异性。完全抑制某些细胞色素P-450同工酶是否没有风险？预期的药物剂量简化难道不会导致需要更多的环孢素A血药浓度检测，从而产生额外费用吗？
