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Pharmacokinetics of pterostilbene in Sprague-Dawley rats: The impacts of aqueous solubility, fasting, dose escalation, and dosing route on bioavailability

Authors


Correspondence: Dr. Hai-Shu Lin, Department of Pharmacy, National University of Singapore, 10 Kent Ridge Crescent, 119260 Singapore

E-mail: phalh@nus.edu.sg

Fax: +65-6779-1554

Abstract

Scope

Pterostilbene (trans-3,5-dimethoxy-4'-hydroxystilbene, PTS) possesses various health-promoting effects. This study aimed to investigate the impacts of aqueous solubility, fasting, dose escalation, and dosing route on its bioavailability in Sprague-Dawley rats.

Methods and results

Upon intravenous administration (2.5 mg/kg), PTS had rapid clearance (Cl = 68.2 ± 9.8 mL/min/kg) and moderate terminal elimination half-life (t1/2λz = 93.9 ± 22.3 min). Dose-escalation led to about twofold decline in clearance at the dose of 25 mg/kg (Cl = 36.4±7.8 mL/min/kg). When given in oral suspension (15 mg/kg), PTS had relatively low bioavailability (F = 15.9 ± 7.8%) while fasting substantially attenuated its bioavailability (F< 5.5 %). However, when dosed in a solution formulated with 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) (15 mg/kg), PTS possessed good bioavailability (F = 59.2 ± 19.6%). Dose escalation resulted in about twofold increase in bioavailability at the dose of 60 mg/kg. Sublingual delivery (2.5 mg/kg) led to rapid absorption and moderate bioavailability (F = 25.8 ± 13.1%). Statistical comparison clearly indicated that the pharmacokinetics of PTS was more favorable than resveratrol.

Conclusion

Aqueous solubility was identified as a barrier to its oral bioavailability while solubilizing PTS with HP-β-CD substantially increased its bioavailability; dose manipulation was a practical strategy to enhance its bioavailability and systemic exposure; and its delivery through oral mucosa was feasible. As PTS possessed superior pharmacokinetics, it is a favorable candidate for further development.

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