A delayed nonlinear PBPK model for genistein dosimetry in rats.
Bull Math Biol
; 69(1): 93-117, 2007 Jan.
Article
em En
| MEDLINE
| ID: mdl-17024552
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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Base de dados:
MEDLINE
Assunto principal:
Genisteína
/
Modelos Biológicos
Idioma:
En
Ano de publicação:
2007
Tipo de documento:
Article