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

Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusions

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.

Keywords

Resveratrol Pterostilbene Pharmacokinetics Bioavailability Metabolites Rat 

Abbreviations

EDTA

Ethylenediaminetetraacetic acid

QC

Quality control

MP

Mobile phase

LLOQ

Lowest limit of quantitation

Tmax

Time to maximum plasma concentration

Cmax

Peak plasma concentration

AUC

Area under the curve

t½

Elimination half-life

CL

Clearance

Vss

Apparent volume of distribution

F%

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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