PMID: 9447653Feb 3, 1998Paper

An introduction to the use of physiologically based pharmacokinetic models in risk assessment

Statistical Methods in Medical Research
A J Bailer, D A Dankovic

Abstract

Many extrapolation issues surface in quantitative risk assessments. The extrapolation from high-dose animal studies to low-dose human exposures is of particular concern. Physiologically based pharmacokinetic (PBPK) models are often proposed as tools to mitigate the problems of extrapolation. These models provide a representation of the disposition, metabolism, and excretion of xenobiotics that are believed to possess the potential of inducing adverse human health responses. Given a model of xenobiotic disposition that is applicable for multiple species and appropriate for nonlinearity of the xenobiotic biotransformation process, better extrapolation may be possible. Unfortunately, the true structure of these models (e.g. number of compartments, type of metabolism, etc.) is seldom known, and attributes of these models (tissue volumes, partition coefficients, etc.) are often experimentally determined and often only central measures of these quantities are reported. We describe the use of PBPK models in risk assessment, the structural and parameter uncertainty in these models, and provide a simple illustration of how these characteristics can be incorporated in a statistical analysis of PBPK models. Additional complexity in the an...Continue Reading

References

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Citations

Apr 24, 2004·Antimicrobial Agents and Chemotherapy·Markus MüllerHartmut Derendorf
Jul 30, 2003·Clinical Pharmacokinetics·Ivan Nestorov
Feb 3, 1998·Statistical Methods in Medical Research·C Portier, H el Masri
Mar 2, 2006·Risk Analysis : an Official Publication of the Society for Risk Analysis·Céline Brochot, Frédéric Y Bois
Dec 22, 2005·Journal of Pharmacokinetics and Pharmacodynamics·Ivelina GueorguievaMalcolm Rowland

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