Steady-State Pharmacokinetics and Tolerability of Trans-Resveratrol 2000mg Twice Daily with Food, Quercetin and Alcohol (Ethanol) in Healthy Human Subjects

• Published in: Clinical pharmacokinetics Vol. 49; no. 7; pp. 449 - 454
• Main Authors: la Porte, Charles, Voduc, Nha, Zhang, Guijun, Seguin, Isabelle, Tardiff, Danielle, Singhal, Neera, Cameron, D. William
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.07.2010
• Subjects: Internal Medicine; Medicine; Medicine & Public Health; Original Research Article; Pharmacology/Toxicology; Pharmacotherapy; Standard Breakfast; Grape Juice; White Wine; Quercetin; Resveratrol
• ISSN: 0312-5963; 1179-1926
• DOI: 10.2165/11531820-000000000-00000

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 100mL 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.