Abstract
Genistein is an endocrine-active compound (EAC) found in soy products. It has been linked to beneficial effects such as mammary tumor growth suppression and adverse endocrine-related effects such as reduced birth weight in rats and humans. In its conjugated form, genistein is excreted in the bile, which is a significant factor in its pharmacokinetics. Experimental data suggest that genistein induces a concentration-dependent suppression of biliary excretion. In this article, we describe a physiologically based pharmacokinetic (PBPK) model that focuses on biliary excretion with the goal of accurately simulating the observed suppression. The mathematical model is a system of nonlinear differential equations with state-dependent delay to describe biliary excretion. The model was analyzed to examine local existence and uniqueness of a solution to the equations. Furthermore, unknown parameters were estimated, and the mathematical model was compared against published experimental data.
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This research was supported by the American Chemistry Council (formerly the Chemical Manufacturers Association, CMA Agreement Reference Number 9121).
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Zager, M.G., Schlosser, P.M. & Tran, H.T. A Delayed Nonlinear PBPK Model for Genistein Dosimetry in Rats. Bull. Math. Biol. 69, 93–117 (2007). https://doi.org/10.1007/s11538-006-9068-x
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DOI: https://doi.org/10.1007/s11538-006-9068-x