Einfluß von Enalapril, Furosemid und Verapamil auf die Ciclosporin-Konzentration im Vollblut

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Abstract
Introduction of ciclosporin A into immunosuppressive therapy is considered a major progress in improving results of organ transplantation. Clinical use of ciclosporin, however, is limited by a low therapeutic index and toxic side effects. Therefore, interactions of ciclosporin with other drugs are clinically important. In our study, we used enalapril, furosemide and verapamil for treatment of arterial hypertension in cardiac transplant recipients and investigated the influence of these drugs on ciclosporin whole blood trough levels. The antihypertensive regimen used in this study normalized blood pressure in each of the 25 patients. Enalapril and furosemide did not influence ciclosporin levels. Adding verapamil, however, resulted in a significant increase of ciclosporin levels, whereas cessation of the drug in one patient treated with verapamil only lowered ciclosporin levels. Thus, when verapamil is introduced or discontinued in patients on ciclosporin, close monitoring of ciclosporin levels and dosage adjustment are necessary. Besides its specific effects verapamil allows reduction of ciclosporin dosage necessary to maintain unaltered levels, which is important regarding cost of therapy. In general, use of any drug with unknown influence on ciclosporin levels requires careful monitoring, even if information exists on other substances of the same group of drugs in this respect. This is especially indicated in drugs known to influence the hepatic cytochrome P450 enzyme system.