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Effect of resveratrol on the pharmacokinetics of carbamazepine in healthy human volunteers

Phytotherapy Research, ISSN: 1099-1573, Vol: 29, Issue: 5, Page: 701-706
2015
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Article Description

The purpose of the present study was to assess the effect of resveratrol (RSV) pretreatment on CYP3A4 enzyme activity and pharmacokinetics of carbamazepine (CBZ) in healthy human volunteers. The open-label, two period, sequential study was conducted in 12 healthy human volunteers. A single dose of RSV 500?mg was administered once daily for 10?days during treatment phase. A single dose of CBZ 200?mg was administered during control and after treatment phases under fasting conditions. The blood samples were collected after CBZ dosing at predetermined time intervals and analyzed by LC-MS/MS. In comparison with the control, RSV pretreatment significantly enhanced maximum plasma concentration (C) area under the curve (AUC), and half life (t) and significantly decreased apparent oral clearance (CL/F) and apparent volume of distribution (Vd/F), while there was no significant change observed in time to reach maximum concentration (t) and elimination rate constant (k) of CBZ. Furthermore, RSV pretreatment significantly decreased metabolite to parent (CBZE/CBZ) ratios of C and AUC and significantly increased CBZE/CBZ ratios of CL/F and Vd/F, indicating the reduced formation of CBZE to CBZ. The results suggest that the altered CYP3A4 enzyme activity and pharmacokinetics of CBZ might be attributed to RSV-mediated inhibition of CYP3A4 enzyme. Thus, there is a potential pharmacokinetic interaction between RSV and CBZ including other CYP3A4 substrates.

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