The Effect of Silibinin on the Pharmacokinetics of Ivabradine and N-Desmethylivabradine in Rats
書誌事項
- 公開日
- 2015
- 権利情報
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- https://www.karger.com/Services/SiteLicenses
- https://www.karger.com/Services/SiteLicenses
- DOI
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- 10.1159/000435890
- 公開者
- S. Karger AG
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説明
<jats:p>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 t1/2, Cmax, AUC(0-t) and AUC(0-∞) 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.</jats:p>
収録刊行物
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- Pharmacology
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Pharmacology 96 (3-4), 107-111, 2015
S. Karger AG