Pharmacokinetic and safety profile of trans-resveratrol in a rising multiple-dose study in healthy volunteers

• Published in: Molecular nutrition & food research Vol. 53; no. S1; pp. S7 - S15
• Main Authors: Almeida, Luis, Vaz-da-Silva, Manuel, Falcão, Amílcar, Soares, Eva, Costa, Raquel, Loureiro, Ana I, Fernandes-Lopes, Carlos, Rocha, José-Francisco, Nunes, Teresa, Wright, Lyndon, Soares-da-Silva, Patrício
• Format: Journal Article
• Language: English
• Published: Weinheim Wiley-VCH Verlag 01.05.2009; WILEY-VCH Verlag; WILEY‐VCH Verlag
• Subjects: administration & dosage; Adult; adverse effects; Bioavailability; Biological Availability; Circadian Rhythm; Double-Blind Method; Female; females; Healthy subjects; Humans; Kinetics; Male; males; Pharmacokinetics; Placebos; Safety; Stilbenes; Stilbenes - administration & dosage; Stilbenes - adverse effects; Stilbenes - pharmacokinetics; Trans-resveratrol; volunteers
• ISSN: 1613-4125; 1613-4133; 1613-4133
• DOI: 10.1002/mnfr.200800177

This was a double-blind, randomised, placebo-controlled study to investigate the pharmacokinetics and safety of trans-resveratrol. In four groups of ten healthy adult subjects (five males and five females), two subjects were randomized to receive placebo and eight subjects to receive trans-resveratrol 25, 50, 100 or 150 mg, six times/day, for thirteen doses. Peak plasma concentrations of trans-resveratrol were reached at 0.8-1.5 h postdose. Following the 13th dose of trans-resveratrol 25, 50, 100 and 150 mg, mean peak plasma concentration (Cmax) was 3.89, 7.39, 23.1 and 63.8 ng/mL and mean area under the plasma concentration-time curve (AUC₀₋τ) was 3.1, 11.2, 33.0 and 78.9 ng·h/mL. Interindividual variability was high, with coefficients of variation >40%. Trans-resveratrol half-life was 1-3 h following single-doses and 2-5 h following repeated dosing. Trough (Cmin) concentrations were [less, not equals]1 ng/mL following 25 and 50 mg, 3 ng/mL following 100 mg and < 10 ng/mL following 150 mg. Trans-resveratrol pharmacokinetics showed circadian variation. Adverse events were mild in severity and similar between all groups. In conclusion, repeated administration was well-tolerated but produced relatively low plasma concentrations of trans-resveratrol, despite the high doses and short dosing interval used. Bioavailability was higher after morning administration.