Steady-State pharmacokinetics and tolerability of trans-resveratrol 2000 mg twice daily with food, quercetin and alcohol (ethanol) in healthy human subjects
BACKGROUND AND OBJECTIVE: Trans-resveratrol is a polyphenol, which is found in red wine and has cancer chemo-preventive properties and disease-preventive properties. The pharmacokinetics of trans-resveratrol have been investigated in single-dose studies and in studies with relatively low dosages. The present study aimed to investigate the steady-state pharmacokinetics and tolerability of trans-resveratrol 2000 mg twice daily with food, quercetin and alcohol (ethanol). METHODS: This was a two-period, open-label, single-arm, within-subject control study in eight healthy subjects. The steady-state 12-hour pharmacokinetics of trans-resveratrol 2000 mg twice daily were studied with a standard breakfast, a high-fat breakfast, quercetin 500 mg twice daily and 5% alcohol 100 mL. Trans-resveratrol plasma concentrations were determined using liquid chromatography with tandem mass spectrometry. RESULTS: The mean (SD) area under the plasma concentration-time curve from 0 to 12 hours (AUC(12)) and maximum plasma concentration (C(max)) of trans-resveratrol were 3558 (2195) ng * h/mL and 1274 (790) ng/mL, respectively, after the standard breakfast. The high-fat breakfast significantly decreased the AUC(12) and C(max) by 45% and 46%, respectively, when compared with the standard breakfast. Quercetin 500 mg twice daily or 5% alcohol 100 mL did not influence trans-resveratrol pharmacokinetics. Diarrhoea was reported in six of the eight subjects. Significant but not clinically relevant changes from baseline were observed in serum potassium and total bilirubin levels. CONCLUSION: Trans-resveratrol 2000 mg twice daily resulted in adequate exposure and was well tolerated by healthy subjects, although diarrhoea was frequently observed. In order to maximize trans-resveratrol exposure, it should be taken with a standard breakfast and not with a high-fat meal. Furthermore, combined intake with quercetin or alcohol did not influence trans-resveratrol exposure.
El transresveratrol es in polifenol el cual se encuentra en el vino tinto y que además tiene propiedades preventivas frente al cáncer. Se han estudiado las propiedades farmacocinéticas del trans-resveratrol en dosis únicas y con dosis relativamente bajas. Este estudio presenta datos sobre la farmacocinética y la tolerancia del trans-resveratrol con 2000 mg dos veces al día acompañado de comida quecertina y alcohol. Esta cantidad de transresveratrol resulta tolerable por los sujetos sanos aunque frecuentemente se observa diarrea. Para mejorar los resultados de la ingesta de transresveratrol debería de tomarse con un desayuno ordinario y una comida no rica en grasas. Además combinado con quecertina o alcohol esto no influye a la ingesta de trans-resveratrol