Effects of Ezetimibe on Cyclosporine Pharmacokinetics in Healthy Subjects

This single-center, open-label, 2-period crossover study investigated the effects of multiple-dose ezetimibe (EZE) on a single dose of cyclosporine (CyA). Healthy subjects received 2 treatments in random order with a 14-day washout: (1) CyA 100 mg alone and (2) EZE 20 mg for 7 days with CyA 100 mg coadministered on day 7; EZE 20 mg alone was administered on day 8. AUC (0-last) and C max geometric mean ratios (90% confidence interval) for ([CyA + EZE]/CyA alone) were 1.15(1.07, 1.25) and 1.10(0.97,1.26), respectively. T max (∼1.3 hours) was similar with and without EZE (P >.200). Mean CyA exposure slightly increased (∼15%) with multiple-dose EZE 20 mg; however, this value was contained within (0.80, 1.25). The implications for chronic EZE dosing within the usual clinical paradigm of chronic CyA dosing have not been established; caution is recommended when using these agents concomitantly. CyA concentrations should be monitored in patients receiving EZE and CyA.