The Effect of Silibinin on the Pharmacokinetics of Ivabradine and N-Desmethylivabradine in Rats

摘要

The objective of this work was to investigate the effect of orally administered silibinin on the pharmacokinetics of ivabradine and its active metabolite N-desmethylivabradine in rats. Twelve healthy male Sprague-Dawley rats were randomly divided into 2 groups: the control group (received oral 1.0 mg/kg ivabradine alone) and the combination group (1.0 mg/kg ivabradine orally coadministered with 30 mg/kg silibinin). The plasma concentration of ivabradine and N-desmethylivabradine were estimated by ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) and different pharmacokinetic parameters were calculated using the DAS 2.0 software. The pharmacokinetic parameters of t(1/2), C-max, AUC((0-t)) and AUC((0-infinity)) of ivabradine in the combination group were significantly higher than those in the control group (p < 0.01). However, silibinin has no effect on the pharmacokinetics of N-desmethylivabradine. This study demonstrates that silibinin increase plasma concentration of ivabradine. Henceforth, the pharmacodynamic influence of this interaction should be taken into consideration while prescribing ivabradine to patients already taking silibinin. (C) 2015 S. Karger AG, Basel