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Open Access Effect of resveratrol on the pharmacokinetics of oral and intravenous nicardipine in rats: possible role of P-glycoprotein inhibition by resveratrol

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Abstract:

The present study aimed to assess the effect of resveratrol on the bioavailability of nicardipine in rats. Nicardipine was administered orally (12 mg kg–1) or intravenously (4 mg kg–1) with or without oral administration of resveratrol (0.5, 2.5 or 10 mg kg–1). The oral administration of 2.5 or 10 mg kg–1 of resveratrol significantly increased both the area under the plasma concentration-time curve (AUC) (P < 0.01, 111–126%) and the peak plasma concentration (Cmax) (P < 0.01, 105–121%), and significantly decreased the total body clearance (CL/F) (P < 0.01, 52.8–55.8%) of orally administered nicardipine. In contrast, resveratrol did not significantly change the pharmacokinetic parameters of i.v. nicardipine. Resveratrol significantly reduced rhodamine123 efflux via P-gp in MCF-7/ADR cells over-expressing P-gp. Resveratrol also inhibits CYP3A4, suggesting that the enhanced oral bioavailability of nicardipine by resveratrol may result from decreased P-gp-mediated efflux or inhibition of intestinal CYP3A4 metabolism. Based on these results, nicardipine dosage should be adjusted when given with supplements containing resveratrol.

Document Type: Research Article

DOI: http://dx.doi.org/10.1691/ph.2008.8683

Affiliations: 1: College of Pharmacy, Chosun University, Gwangju, Korea 2: College of Pharmacy, Chosun University, 375 Seosuk-Dong, Dong-Gu, Gwangju, Korea, Email: kwkang@chosun.ac.kr

Publication date: January 1, 2009

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  • Pharmazie is a leading journal in the field of pharmaceutical sciences. As a peer-reviewed scientific journal, Pharmazie is regularly indexed in the relevant databases like Web of science, Journal Citation Reports and many others. The journal is open for submissions from the whole spectrum of pharnaceutical sciences including Pharmaceutical Chemistry, Experimental and Clinical Pharmacology, Drug Analysis, Pharmaceutics, Pharmaceutical Biology, Clinical Pharmacy etc.
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