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Effect of Resveratrol on the Pharmacokinetics of Carbamazepine in Healthy Human Volunteers
Author(s) -
Bedada Satish Kumar,
Nearati Prasad
Publication year - 2015
Publication title -
phytotherapy research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.019
H-Index - 129
eISSN - 1099-1573
pISSN - 0951-418X
DOI - 10.1002/ptr.5302
Subject(s) - pharmacokinetics , cmax , pharmacology , carbamazepine , cyp3a4 , volume of distribution , metabolite , anticonvulsant , active metabolite , chemistry , elimination rate constant , area under the curve , oral administration , medicine , enzyme , epilepsy , biochemistry , cytochrome p450 , psychiatry
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 max ) , area under the curve (AUC), and half life (t 1/2 ) 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 max ) and elimination rate constant (k el ) of CBZ. Furthermore, RSV pretreatment significantly decreased metabolite to parent (CBZE/CBZ) ratios of C max 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. Copyright © 2015 John Wiley & Sons, Ltd.