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Developmental and Life-Stage Physiologically-Based Pharmacokinetic (PBPK) Models in Humans and Animal Models.
Citation:
El-Masri, H. Developmental and Life-Stage Physiologically-Based Pharmacokinetic (PBPK) Models in Humans and Animal Models. Society of Toxicology, San Antonio, Texas, March 11 - 15, 2018.
Impact/Purpose:
This presentation will increase the knowledge of the at-large toxicology community on :1) development and application of computational methods to toxicology, 2) physiological and biochemical factors that impact tissue distribution of chemicals during pregnancy and fetal stages of life. The intent is for the attendees to become more familiar with computational methods, specifically, physiologically-based pharmacokinetic (PBPK) models, and their applications to toxicological research during different life-stages.
Description:
PBPK models provide a computational framework for incorporating pertinent physiological and biochemical information to estimate in vivo levels of xenobiotics in biological tissues. In general, PBPK models are used to correlate exposures to target tissue levels of chemicals and their metabolites which, in turn, are related to toxicological endpoints. PBPK models are specifically useful in assessing risks of xenobiotics to a developing fetus or nursing pups because of their applications to provide time and dose-course predictions during gestation covering critical windows of susceptibilities during development. This lecture starts with covering basics of PBPK models structures and applications. Physiological and biochemical process impacting tissue dosimetry of xenobiotics during gestation, fetal and early-life stage development will be addressed. Quantitative descriptions and inclusion of these biological processes in PBPK models will be illustrated using several examples from literature where developmental and life-stage PBPK were applied to xenobiotics.