Steady-State Pharmacokinetics and Tolerability of Trans-Resveratrol 2000 mg 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: Auckland Adis International 01.07.2010; Wolters Kluwer Health, Inc; Springer Nature B.V
• Subjects: Adult; Alcohol; Alcohol, Denatured; Area Under Curve; Biological and medical sciences; Chromatography, Liquid; Diarrhea - chemically induced; Diet; Dosage and administration; Drug Administration Schedule; Drug Combinations; Drug Tolerance; Ethanol - administration & dosage; Ethanol - pharmacology; Female; General pharmacology; Health aspects; Humans; Liquid chromatography; Male; Mass spectrometry; Medical sciences; Methods; Middle Aged; Pharmacokinetics; Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions; Pharmacology. Drug treatments; Quercetin; Quercetin - administration & dosage; Quercetin - pharmacology; Resveratrol; Stilbenes - administration & dosage; Stilbenes - blood; Stilbenes - pharmacokinetics; Tandem Mass Spectrometry; Canada; Human; Ethanol; Healthy subject; Toxicity; Antioxidant; Flavonoid; Stilbene derivatives; Alcoholic beverage; Polyphenol; Phytoalexin; Quercetin; Resveratrol; Phenols; Pharmacokinetics; Food
• ISSN: 0312-5963; 1179-1926; 1179-1926
• DOI: 10.2165/11531820-000000000-00000

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). 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. 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. 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.