title: Pharmacokinetics of pterostilbene in Sprague-Dawley rats: the impacts of aqueous solubility, fasting, dose escalation, and dosing route on bioavailability.
abstract: METHODS
  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.
  
  
  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 (t(1/2λz) = 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.
  
  
  CONCLUSIONS
  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.
authors: Department of Pharmacy, National University of Singapore, Singapore.
authors: Samuel Chao Ming
authors: SC
authors: Yeo
authors: Paul C
authors: PC
authors: Ho
authors: Hai-Shu
authors: HS
authors: Lin
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D061605:Administration, Intravenous; D000284:Administration, Oral; D000286:Administration, Sublingual; D000818:Animals; D001682:Biological Availability; D004305:Dose-Response Relationship, Drug; D005215:Fasting; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013267:Stilbenes / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D047392:beta-Cyclodextrins / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D013267:Stilbenes; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; C107773:pterostilbene