Pharmacokinetics and tissue distribution of pterostilbene in the rat

Pterostilbene (Pt) is emerging as an important health-promoting natural compound. Pharmacokinetic studies so far have focused on plasma levels, while Pt distribution in tissues is most relevant for biological action. This study determined tissue distribution of Pt and its major metabolite, pterostilbene-4'-sulfate (Pt-S), in rats after oral administration.

Upon intravenous (iv) administration (88 μmol/kg), Pt was cleared from blood with a half-life of 1.8 ± 0.3 h. Oral administration (same dose) resulted in moderate Pt bioavailability (∼35%) and in an increased abundance of Pt-S in blood (AUC(Pt)/AUC(Pt-S) ∼0.75 and ∼0.05 after iv or oral administration, respectively). Pt-S was the major species in all organs except the brain, where intact Pt was predominant (AUC(Pt)/AUC(Pt-S) ∼5). Both Pt and Pt-S peaked in all tissues at approximately 2 h. The highest levels (∼200 nmoles/g for Pt-S and 40 nmoles/g for Pt) were measured in the liver, the lowest (≤7 nmol/g) in skeletal muscles and testes.

AUC(Pt) was ∼2- to ∼25-fold higher in tissues than in blood; this may explain its bioactivity despite barely detectable blood levels. Of particular interest is the high fraction of nonmetabolized Pt in the brain, given the reports of its activity at the level of the central nervous system.