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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

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Record number 478655
Title A physiologically based kinetic (PBK) model describing plasma concentrations of quercetin and its metabolites in rats
Author(s) Boonpawa, R.; Spenkelink, A.; Rietjens, I.; Punt, A.
Source Biochemical Pharmacology 89 (2014)2. - ISSN 0006-2952 - p. 287 - 299.
DOI https://doi.org/10.1016/j.bcp.2014.02.007
Department(s) Toxicology
VLAG
Publication type Refereed Article in a scientific journal
Publication year 2014
Keyword(s) flavonoid-mediated inhibition - blood partition-coefficients - oral bioavailability - biological-activity - biliary-excretion - intestinal uptake - glucuronidation - humans - absorption - tissues
Abstract Biological activities of flavonoids in vivo are ultimately dependent on the systemic bioavailability of the aglycones as well as their metabolites. In the present study, a physiologically based kinetic (PBK) model was developed to predict plasma concentrations of the flavonoid quercetin and its metabolites and to tentatively identify the regiospecificity of the major circulating metabolites. The model was developed based on in vitro metabolic parameters and by fitting kinetic parameters to literature available in vivo data. Both exposure to quercetin aglycone and to quercetin-4'-O-glucoside, for which in vivo data were available, were simulated. The predicted plasma concentrations of different metabolites adequately matched literature reported plasma concentrations of these metabolites in rats exposed to 4'-O-glucoside. The bioavailability of aglycone was predicted to be very low ranging from 0.004%-0.1% at different oral doses of quercetin or quercetin-4'-O-glucoside. Glucuronidation was a crucial pathway that limited the bioavailability of the aglycone, with 95–99% of the dose being converted to monoglucuronides within 1.5–2.5 h at different dose levels ranging from 0.1 to 50 mg/kg bw quercetin or quercetin-4'-O-glucoside. The fast metabolic conversion to monoglucuronides allowed these metabolites to further conjugate to di- and tri-conjugates. The regiospecificity of major circulating metabolites was observed to be dose-dependent. As we still lack in vivo kinetic data for many flavonoids, the developed model has a great potential to be used as a platform to build PBK models for other flavonoids as well as to predict the kinetics of flavonoids in humans.
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