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Steady-State Pharmacokinetics and Tolerability of Trans-Resveratrol 2000mg Twice Daily with Food, Quercetin and Alcohol (Ethanol) in Healthy Human Subjects

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Abstract

Background and 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 (AUC12) and maximum plasma concentration (Cmax) 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 AUC12 and Cmax by 45% and 46%, respectively, when compared with the standard breakfast. Quercetin 500 mg twice daily or 5% alcohol 100mL 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.

Conclusion

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.

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Acknowledgements

The healthy subjects are gratefully acknowledged for their participation in this study. D. William Cameron is supported by a Career Scientist Award from the Ontario Ministry of Health/Ontario HIV Treatment Network. No sources of funding were used for the conduct of this study or preparation of this manuscript. The authors have no conflicts of interest that are directly relevant to the content of this study.

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Authors and Affiliations

  1. The Ottawa Hospital Research Institute, 501 Smyth Road, Mailbox 223, Ottawa, Ontario, K1H 8L6, Canada

    Charles la Porte, Guijun Zhang, Isabelle Seguin, Danielle Tardiff, Neera Singhal & D. William Cameron

  2. University of Ottawa, Ottawa, Ontario, Canada

    Charles la Porte, Nha Voduc, Neera Singhal & D. William Cameron

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  1. Charles la Porte
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  2. Nha Voduc
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  3. Guijun Zhang
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  4. Isabelle Seguin
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  5. Danielle Tardiff
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  6. Neera Singhal
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  7. D. William Cameron
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Correspondence to Charles la Porte.

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la Porte, C., Voduc, N., Zhang, G. et al. Steady-State Pharmacokinetics and Tolerability of Trans-Resveratrol 2000mg Twice Daily with Food, Quercetin and Alcohol (Ethanol) in Healthy Human Subjects. Clin Pharmacokinet 49, 449–454 (2010). https://doi.org/10.2165/11531820-000000000-00000

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