This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Boocock, D. J. Articles by Brenner, D. E. Search for Related Content PubMed PubMed Citation Articles by Boocock, D. J. Articles by Brenner, D. E. Related Collections Clinical Intervention Clinical Intervention: Early-Phase (I/II) Clinical or Translational Trials

Phase I Dose Escalation Pharmacokinetic Study in Healthy Volunteers of Resveratrol, a Potential Cancer Chemopreventive Agent

¹ Cancer Biomarkers and Prevention Group, Department of Cancer Studies and Molecular Medicine, Leicester University, Leicester, United Kingdom; ² MDS Pharma Services; ³ Royalmount Pharma, Montreal, Canada; ⁴ Chemopreventive Agent Development Research Group, National Cancer Institute, Bethesda, Maryland; and ⁵ Departments of Internal Medicine and Pharmacology, University of Michigan Medical School and VA Medical Center, Ann Arbor, Michigan

Requests for reprints: Andreas J. Gescher, Department of Cancer Studies and Molecular Medicine, Leicester Royal Infirmary, Robert Kilpatrick Clinical Sciences Building, Leicester University, Leicester LE2 7LX, United Kingdom; Phone: 44-116-223-1856; Fax: 44-116-223-1855. E-mail: ag15{at}le.ac.uk

The red grape constituent resveratrol possesses cancer chemopreventive properties in rodents. The hypothesis was tested that, in healthy humans, p.o. administration of resveratrol is safe and results in measurable plasma levels of resveratrol. A phase I study of oral resveratrol (single doses of 0.5, 1, 2.5, or 5 g) was conducted in 10 healthy volunteers per dose level. Resveratrol and its metabolites were identified in plasma and urine by high-performance liquid chromatography-tandem mass spectrometry and quantitated by high-performance liquid chromatography-UV. Consumption of resveratrol did not cause serious adverse events. Resveratrol and six metabolites were recovered from plasma and urine. Peak plasma levels of resveratrol at the highest dose were 539 ± 384 ng/mL (2.4 µmol/L, mean ± SD; n = 10), which occurred 1.5 h post-dose. Peak levels of two monoglucuronides and resveratrol-3-sulfate were 3- to 8-fold higher. The area under the plasma concentration curve (AUC) values for resveratrol-3-sulfate and resveratrol monoglucuronides were up to 23 times greater than those of resveratrol. Urinary excretion of resveratrol and its metabolites was rapid, with 77% of all urinary agent-derived species excreted within 4 h after the lowest dose. Cancer chemopreventive effects of resveratrol in cells in vitro require levels of at least 5 µmol/L. The results presented here intimate that consumption of high-dose resveratrol might be insufficient to elicit systemic levels commensurate with cancer chemopreventive efficacy. However, the high systemic levels of resveratrol conjugate metabolites suggest that their cancer chemopreventive properties warrant investigation. (Cancer Epidemiol Biomarkers Prev 2007;16(6):1246–52)

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]

				N. F. Trincheri, C. Follo, G. Nicotra, C. Peracchio, R. Castino, and C. Isidoro Resveratrol-induced apoptosis depends on the lipid kinase activity of Vps34 and on the formation of autophagolysosomes Carcinogenesis, February 1, 2008; 29(2): 381 - 389. [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]

				E. H. Heiss, Y. D. C. Schilder, and V. M. Dirsch Chronic Treatment with Resveratrol Induces Redox Stress- and Ataxia Telangiectasia-mutated (ATM)-dependent Senescence in p53-positive Cancer Cells J. Biol. Chem., September 14, 2007; 282(37): 26759 - 26766. [Abstract] [Full Text] [PDF]