Physiologically Based Pharmacokinetic Model for 2,3,7,8-Tetrabromodibenzo-p-Dioxin (TBDD) in the Rat: Tissue Distribution and CYP1A Induction

摘要

Biologically based models serve as valuable tools for integration of mechanistic pharmacokinetic data by their explicit definition of important determinants of chemical disposition. The objective of the present work was to develop a physiologically based pharmacokinetic model to describe the disposition and enzyme induction properties of 2,3,7,8-tetrabromodibenzo-p-dioxin (TBDD). The TBDD model, which was based on models previously developed for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), incorporated: ternary interactions between TBDD, the Ah receptor, and specific DNA-binding sites; induction of a TBDD-binding protein specific to the liver; and diffusion-limited tissue uptake. (Copyright (c) 1993 by Academic Press, Inc.)