Using structural information to create physiologically based pharmacokinetic models for all polychlorinated biphenyls. II. Rates of metabolism.

F M Parham; C J Portier

doi:10.1006/taap.1998.8441

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Using structural information to create physiologically based pharmacokinetic models for all polychlorinated biphenyls. II. Rates of metabolism.

F M Parham·C J Portier

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Abstract

Physiologically based pharmacokinetic (PBPK) models are useful in describing the distribution, metabolism, and fate of xenobiotics across multiple species. The eventual goal of the present research is to create PBPK models for all 209 polychlorinated biphenyls (PCBs). Key parameters in any PBPK model are the metabolic rates. Data on metabolic rates of PCBs were derived from in vitro experiments and from fitting of PBPK models to in vivo data. The rate of metabolism was assumed to be a linear function of PCB concentration. Structural descriptors suggested by the literature were used in a stepwise regression to find an expression for the metabolic rate of PCBs as a function of five structural descriptors related to the degree and pattern of chlorine substitution. R2 for the fit of the model to the data is 0.9606.

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Animals In Vitro Techniques Male Metabolic Clearance Rate Models, Biological Polychlorinated Biphenyls Rats Regression Analysis Structure-Activity Relationship Tissue Distribution Journal Article

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F M Parham, C J Portier. 1998. Using structural information to create physiologically based pharmacokinetic models for all polychlorinated biphenyls. II. Rates of metabolism.. https://doi.org/10.1006/taap.1998.8441

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