![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
|
|
|
|
|
||
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Received for publication June 8, 2004.
Revised August 25, 2004.
Accepted for publication August 26, 2004.
The dietary polyphenol resveratrol has been shown to have chemopreventive activity against cardiovascular disease and a variety of cancers in model systems, but it is not clear whether the drug reaches the proposed sites of action in vivo after oral ingestion, especially in humans. In this study, we examined the absorption, bioavailability and metabolism of [14C]resveratrol after oral and i.v. doses in six human volunteers. The absorption of a dietary relevant 25-mg oral dose was at least 70% with peak plasma levels of resveratrol and metabolites of 491 ± 90 ng/ml (about 2 µM) and a plasma half-life of 9.2 ± 0.6 h. However, only trace amounts of unchanged resveratrol (< 5 ng/ml) could be detected in plasma. Most of the oral dose was recovered in urine and LC/MS analysis identified three metabolic pathways, i.e. sulfate and glucuronic acid conjugation of the phenolic groups and, interestingly, hydrogenation of the aliphatic double bond, the latter likely produced by the intestinal microflora. Extremely rapid sulfate conjugation by the intestine/liver appears to be the rate-limiting step in resveratrol's bioavailability. Although the systemic bioavailability of resveratrol is very low, accumulation of resveratrol in epithelial cells along the aerodigestive tract and potentially active resveratrol metabolites may still produce cancer preventive and other effects.
Key words:
absorption, anticancer agents, bioavailability, chemoprotection, drug disposition, glucuronidation, human pharmacokinetics, oral absorption, structure elucidation, sulfate conjugation
This article has been cited by other articles:
|
|
 |
|
  O. F. Iwuchukwu and S. Nagar Resveratrol (trans-Resveratrol, 3,5,4'-Trihydroxy-trans-stilbene) Glucuronidation Exhibits Atypical Enzyme Kinetics in Various Protein Sources Drug Metab. Dispos., February 1, 2008; 36(2): 322 - 330. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Furimsky, C. E. Green, L. E. H. Sharp, P. Catz, A. A. Adjei, T. Parman, I. M. Kapetanovic, R. M. Weinshilboum, and L. V. Iyer Effect of Resveratrol on 17 -Estradiol Sulfation by Human Hepatic and Jejunal S9 and Recombinant Sulfotransferase 1E1 Drug Metab. Dispos., January 1, 2008; 36(1): 129 - 136. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. J. Boocock, G. E.S. Faust, K. R. Patel, A. M. Schinas, V. A. Brown, M. P. Ducharme, T. D. Booth, J. A. Crowell, M. Perloff, A. J. Gescher, et al. Phase I Dose Escalation Pharmacokinetic Study in Healthy Volunteers of Resveratrol, a Potential Cancer Chemopreventive Agent Cancer Epidemiol. Biomarkers Prev., June 1, 2007; 16(6): 1246 - 1252. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Lancon, N. Hanet, B. Jannin, D. Delmas, J.-M. Heydel, G. Lizard, M.-C. Chagnon, Y. Artur, and N. Latruffe Resveratrol in Human Hepatoma HepG2 Cells: Metabolism and Inducibility of Detoxifying Enzymes Drug Metab. Dispos., May 1, 2007; 35(5): 699 - 703. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Ung and S. Nagar Variable Sulfation of Dietary Polyphenols by Recombinant Human Sulfotransferase (SULT) 1A1 Genetic Variants and SULT1E1 Drug Metab. Dispos., May 1, 2007; 35(5): 740 - 746. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Urpi-Sarda, R. Zamora-Ros, R. Lamuela-Raventos, A. Cherubini, O. Jauregui, R. de la Torre, M. I. Covas, R. Estruch, W. Jaeger, and C. Andres-Lacueva HPLC-Tandem Mass Spectrometric Method to Characterize Resveratrol Metabolism in Humans Clin. Chem., February 1, 2007; 53(2): 292 - 299. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Wen and T. Walle Methylated Flavonoids Have Greatly Improved Intestinal Absorption and Metabolic Stability Drug Metab. Dispos., October 1, 2006; 34(10): 1786 - 1792. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. A. Tsuji and T. Walle Inhibition of benzo[a]pyrene-activating enzymes and DNA binding in human bronchial epithelial BEAS-2B cells by methoxylated flavonoids Carcinogenesis, August 1, 2006; 27(8): 1579 - 1585. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Zamora-Ros, M. Urpi-Sarda, R. M. Lamuela-Raventos, R. Estruch, M. Vazquez-Agell, M. Serrano-Martinez, W. Jaeger, and C. Andres-Lacueva Diagnostic Performance of Urinary Resveratrol Metabolites as a Biomarker of Moderate Wine Consumption Clin. Chem., July 1, 2006; 52(7): 1373 - 1380. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. M. Harris, E. Besselink, S. M. Henning, V. L. W. Go, and D. Heber Phytoestrogens Induce Differential Estrogen Receptor Alpha- or Beta-Mediated Responses in Transfected Breast Cancer Cells Experimental Biology and Medicine, September 1, 2005; 230(8): 558 - 568. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
