Cyclosporin and ketoconazole, drug interaction or therapeutic association?

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.