Physiologically based pharmacokinetic (PB-PK) models in the study of the disposition and biological effects of xenobiotics and drugs

Abstract

Physiologically based pharmacokinetic (PB-PK) models have been used to study the mechanisms of disposition of drugs and xenobiotics for almost 70 years. Their widespread application in toxicology began 15 years ago with models for polychlorinated biphenyls and other persistent lipophilic compounds. Quantitative applications of PB-PK models in carcinogen risk assessment date to the development of a number of PB-PK models for dichloromethane in the mid 1980s. The expanding use of these models is primarily related to their ability to make more accurate predictions of target tissue dose for different exposure situations in different animal species. including humans and to evaluate quantitatively the mechanisms of disposition of chemicals within the body. This paper discusses contemporary uses of PB-PK modeling in the context of risk assessment with xenobiotics and of safety assessment with drugs.