The Impact of Aqueous Solubility and Dose on the Pharmacokinetic Profiles of Resveratrol

Purpose  This study aimed at the investigation of the impact of aqueous solubility and dose manipulation on the pharmacokinetics of resveratrol. Methods  Water soluble intravenous and oral formulations of resveratrol were prepared with hydroxypropyl-β-cyclodextrin (HP-β-CD) and randomly methylated-β-cyclodextrin (RM-β-CD), respectively. Sodium salt and suspension of resveratrol in carboxymethyl cellulose (CMC) were used as the reference intravenous and oral formulations, respectively. The pharmacokinetics of resveratrol was assessed in Sprague–Dawley rats. Plasma resveratrol concentrations were measured by high performance liquid chromatography (HPLC). Results  Both HP-β-CD and RM-β-CD enhanced the aqueous solubility of resveratrol. After intravenous administration, rapid elimination of resveratrol was observed at all tested doses (5, 10, and 25 mg kg⁻¹) regardless of formulation types; with non-linear elimination occurring at the dose of 25 mg kg⁻¹. RM-β-CD significantly increased the maximal plasma concentration of orally administered resveratrol, but, it did not increase the oral bioavailability in comparison with the CMC suspension. Furthermore, the oral bioavailability remained unchanged among all tested doses (15, 25, and 50 mg kg⁻¹). Conclusions  Aqueous solubility barrier might affect the speed but not the extent of resveratrol absorption. Further, dose manipulation (up to 50 mg kg⁻¹) did not have a significant impact on the oral bioavailability of resveratrol. An erratum to this article can be found at