Nicolau D P, Uber W E, Crumbley A J, Strange C
Department of Hospital Pharmacy Practice and Administration, Medical University of South Carolina, Charleston 29425-0810.
J Heart Lung Transplant. 1992 May-Jun;11(3 Pt 1):564-8.
We report the case of a heart transplant patient whose cyclosporine clearance decreased by more than 50% after the institution of amiodarone therapy. This interaction necessitated a significant dosage reduction to maintain cyclosporine concentrations within the therapeutic range. To investigate the mechanism of the interaction, a cyclosporine-lipoprotein-binding determination was performed. The results suggest that drug displacement from competitive lipoprotein-binding sites is not responsible for the alterations in cyclosporine pharmacokinetics. Clearance data suggests, however, that the primary mechanism for the interaction is the inhibition cyclosporine metabolism by the cytochrome P-450 system. This report emphasizes the importance of reevaluating therapeutic drug regimens when new agents are added to prevent complications caused by drug interactions. If amiodarone and cyclosporine must be used concomitantly, cyclosporine levels must be monitored frequently, in anticipation of this interaction.
我们报告了一例心脏移植患者，在使用胺碘酮治疗后，其环孢素清除率下降了50%以上。这种相互作用使得必须大幅减少环孢素剂量，以将其浓度维持在治疗范围内。为了研究这种相互作用的机制，进行了环孢素-脂蛋白结合测定。结果表明，竞争性脂蛋白结合位点的药物置换并非环孢素药代动力学改变的原因。然而，清除率数据表明，这种相互作用的主要机制是细胞色素P-450系统对环孢素代谢的抑制作用。本报告强调，当添加新药物时重新评估治疗药物方案以预防药物相互作用引起的并发症的重要性。如果必须同时使用胺碘酮和环孢素，鉴于这种相互作用，必须频繁监测环孢素水平。
