Cancer Chemotherapy and Pharmacology

, Volume 68, Issue 3, pp 593–601

Pharmacokinetics, oral bioavailability, and metabolic profile of resveratrol and its dimethylether analog, pterostilbene, in rats

  • Izet M. Kapetanovic
  • Miguel Muzzio
  • Zhihua Huang
  • Thomas N. Thompson
  • David L. McCormick
Original Article

DOI: 10.1007/s00280-010-1525-4

Cite this article as:
Kapetanovic, I.M., Muzzio, M., Huang, Z. et al. Cancer Chemother Pharmacol (2011) 68: 593. doi:10.1007/s00280-010-1525-4



Resveratrol (3,5,4′-trihydroxy-trans-stilbene) is a naturally occurring polyphenol with a broad range of possible health benefits, including anti-cancer activity. However, the biological activity of resveratrol may be limited by poor absorption and first-pass metabolism: only low plasma concentrations of resveratrol are seen following oral administration, and metabolism to glucuronide and sulfate conjugates is rapid. Methylated polyphenol analogs (such as pterostilbene [3,5-dimethoxy-4′-hydroxy-trans-stilbene], the dimethylether analog of resveratrol) may overcome these limitations to pharmacologic efficacy. The present study was designed to compare the bioavailability, pharmacokinetics, and metabolism of resveratrol and pterostilbene following equimolar oral dosing in rats.


The agents were administered orally via gavage for 14 consecutive days at 50 or 150 mg/kg/day for resveratrol and 56 or 168 mg/kg/day for pterostilbene. Two additional groups were dosed once intravenously with 10 and 11.2 mg/kg for resveratrol and pterostilbene, respectively. Plasma concentrations of agents and metabolites were measured using a high-pressure liquid chromatograph-tandem mass spectrometer system. Noncompartmental analysis was used to derive pharmacokinetic parameters.


Resveratrol and pterostilbene were approximately 20 and 80% bioavailable, respectively. Following oral dosing, plasma levels of pterostilbene and pterostilbene sulfate were markedly greater than were plasma levels of resveratrol and resveratrol sulfate. Although plasma levels of resveratrol glucuronide exceeded those of pterostilbene glucuronide, those differences were smaller than those of the parent drugs and sulfate metabolites.


When administered orally, pterostilbene demonstrates greater bioavailability and total plasma levels of both the parent compound and metabolites than does resveratrol. These differences in agent pharmacokinetics suggest that the in vivo biological activity of equimolar doses of pterostilbene may be greater than that of resveratrol.


Resveratrol Pterostilbene Pharmacokinetics Bioavailability Metabolites Rat 



Ethylenediaminetetraacetic acid


Quality control


Mobile phase


Lowest limit of quantitation


Time to maximum plasma concentration


Peak plasma concentration


Area under the curve


Elimination half-life




Apparent volume of distribution


Percent bioavailability

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Izet M. Kapetanovic
    • 1
  • Miguel Muzzio
    • 2
  • Zhihua Huang
    • 2
  • Thomas N. Thompson
    • 3
  • David L. McCormick
    • 2
  1. 1.Division of Cancer PreventionNational Cancer InstituteBethesdaUSA
  2. 2.Life Sciences GroupIIT Research InstituteChicagoUSA
  3. 3.R&D Services Pharma ConsultingOmahaUSA

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