Albengres E, Tillement J P
Service Hospitalo-Universitaire de Pharmacologie, UFR de Médecine de Paris XII, Hôpital Intercommunal, Créteil, France.
Int J Clin Pharmacol Ther Toxicol. 1992 Dec;30(12):555-70.
Coadministration of cyclosporin and ketoconazole results in marked elevation in blood levels of cyclosporin, which is believed to be the result of competition for hepatic P-450 mixed function oxidase enzymes. This requires a significant reduction in cyclosporin dosage regimen which may result in savings of nearly $5,000/year per transplant recipient. As a consequence, the idea of intentionally adding ketoconazole to cyclosporin for the purpose of decreasing toxicity and cost has been advanced. This article reviews the reported cases and studies of which the ketoconazole/cyclosporin interaction is the major concern. From a pharmaceutical standpoint, it is stressed that further investigations are needed to clarify the actual consequences of the inhibitory effect of ketoconazole on cyclosporin metabolism as well in short-term as in long-term treatments, before taking advantage of metabolic interaction to supply the two drugs as a unique preparation for clinical use. It is concluded that at the time of this review, individual monitoring of adjunctive ketoconazole therapy still remains the best therapeutic choice.
环孢素与酮康唑合用时，会导致环孢素血药浓度显著升高，这被认为是二者竞争肝P - 450混合功能氧化酶的结果。这就需要大幅减少环孢素的用药方案，这可能会使每位移植受者每年节省近5000美元。因此，有人提出为降低毒性和成本而有意将酮康唑添加到环孢素中的想法。本文回顾了以酮康唑/环孢素相互作用为主要关注点的报告病例和研究。从药学角度强调，在利用代谢相互作用将这两种药物制成单一临床制剂之前，需要进一步研究以明确酮康唑对环孢素代谢抑制作用在短期和长期治疗中的实际后果。结论是，在本次综述时，对酮康唑辅助治疗进行个体监测仍然是最佳治疗选择。
