Pharmacokinetic and safety profile of trans-resveratrol in a rising multiple-dose study in healthy volunteers.
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 (C(max)) was 3.89, 7.39, 23.1 and 63.8 ng/mL and mean area under the plasma concentration-time curve (AUC(0-tau)) 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 (C(min)) concentrations were < or = 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.
Almeida
Luis
L
Department of Research and Development, BIAL-Portela & Co SA, S Mamede do Coronado, Portugal.
Vaz-da-Silva
Manuel
M
Falcão
Amílcar
A
Soares
Eva
E
Costa
Raquel
R
Loureiro
Ana I
AI
Fernandes-Lopes
Carlos
C
Rocha
José-Francisco
JF
Nunes
Teresa
T
Wright
Lyndon
L
Soares-da-Silva
Patrício
P
D000328:Adult; D001682:Biological Availability; D002940:Circadian Rhythm; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007700:Kinetics; D008297:Male; D010919:Placebos; D000077185:Resveratrol; D013267:Stilbenes / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*
D010919:Placebos; D013267:Stilbenes; D000077185:Resveratrol