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

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An Erratum to this article was published on 23 August 2008

Abstract

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.

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Abbreviations

AUC:

area under curve

C max :

maximum plasma concentration

CD:

cyclodextrin

Cl:

clearance

CMC:

carboxy methyl cellulose

F :

bioavailability

HP-β-CD:

hydroxypropyl-β-cyclodextrin

HPLC:

high performance liquid chromatography

LOQ:

limit of quantitation

PBS:

phosphate buffer solution

RM-β-CD:

randomly methylated-β-cyclodextrin

SGF:

simulated gastric fluid

SIF:

simulated intestinal fluid

T max :

time to reach C max

t 1/2 :

half life

V :

volume of distribution

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Acknowledgments

This work was partially supported through a National University of Singapore Academic Research Fund R148-050-068-101 and R148-050-068-133 (K. Ng) and NIH grant R21 CA 115269 (K. Ng).

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Authors and Affiliations

  1. Department of Pharmacy, Faculty of Science, National University of Singapore, Building S4, Rm 05-02, 18 Science Drive 4, Singapore, 117543, Singapore

    Surajit Das, Hai-Shu Lin, Paul C. Ho & Ka-Yun Ng

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Correspondence to Ka-Yun Ng.

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An erratum to this article can be found at http://dx.doi.org/10.1007/s11095-008-9701-5

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Das, S., Lin, HS., Ho, P.C. et al. The Impact of Aqueous Solubility and Dose on the Pharmacokinetic Profiles of Resveratrol. Pharm Res 25, 2593–2600 (2008). https://doi.org/10.1007/s11095-008-9677-1

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