Steady-State pharmacokinetics and tolerability of trans-resveratrol 2000 mg twice daily with food, quercetin and alcohol (ethanol) in healthy human subjects.
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 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.


CONCLUSIONS
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.
la Porte
Charles
C
Ottawa Hospital Research Institute, Ottawa, Ontario K1H 8L6, Canada. claporte@ohri.ca
Voduc
Nha
N
Zhang
Guijun
G
Seguin
Isabelle
I
Tardiff
Danielle
D
Singhal
Neera
N
Cameron
D William
DW
D000328:Adult; D019540:Area Under Curve; D002853:Chromatography, Liquid; D003967:Diarrhea / Q000139:chemically induced; D004032:Diet; D004334:Drug Administration Schedule; D004338:Drug Combinations; D004361:Drug Tolerance; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010599:Pharmacokinetics; D011794:Quercetin / Q000008:administration & dosage / Q000494:pharmacology*; D000077185:Resveratrol; D013267:Stilbenes / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D053719:Tandem Mass Spectrometry
D004338:Drug Combinations; D013267:Stilbenes; D000431:Ethanol; D011794:Quercetin; D000077185:Resveratrol