生物等效性和生物利用度杂志

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Resveratrol Enhances the Bioavailability of Fexofenadine in Healthy Human Male Volunteers: Involvement of P-Glycoprotein Inhibition

Satish Kumar Bedada, Sudhakar Akul Yakkanti and Prasad Neerati

Objective: The purpose of the present study was to assess the influence ofresveratrol onP-glycoprotein mediated drug disposition in humans using fexofenadine as a P-glycoprotein substrate. Methods: A non-blinded, an open label crossover study was conducted in twelve healthy male volunteers aged between 26 and 31 years. A single dose of fexofenadine hydrochloride 120 mg was given to volunteers during control phase and treatment phases. A single dose of resveratrol 500 mg was given to volunteers once daily for period of 10 days. The blood samples were collected at predetermined time intervals during control and treatment phases. The plasma samples containing fexofenadine hydrochloridewere analyzed by LC-MS/MS. The pharmacokinetic parameters were computed by non-compartmental method and the mean pharmacokinetic parameter differences during control and treatment phases were assessed. Results: Treatment with resveratrol significantly increased thearea under the plasma concentration-time curve (AUC) and maximum plasma concentration (Cmax) offexofenadine to 76.7%(2520.92.48 versus 4454.48 ng.h/mL) and 65.2% (415.08 versus 685.58 ng/mL)respectively when compared to control phase. On other hand, apparentoral clearance (CL/F) and apparent volume of distribution (Vd/F) of fexofenadine were significantly decreased by 42.6% (49.46 versus 28.37 L/h) and 42.1 % (591.73 versus 342.62 L) respectively. However, there was no significant change was observed in T1/2, Kel and Tmaxof fexofenadine upon treatment with resveratrol when compared to control phase. Conclusion: The results of the present study showed that multiple doses of resveratrolenhanced the bioavailability of fexofenadine probably by the inhibition of P-glycoprotein mediated drug efflux in humans.