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

Abstract

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 (AUC 0‐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 ⪇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.