Although certain physiological aspects of disposition of substances by organs within the body had received atten-tion earlier, it was in 1937, with the seminal work of Teorell, that an integrated approach to whole body physiologically based modeling of pharmacokinetics received first serious attention. However, owing to the resultant mathematical and computational complexities and the lack of some basic physiological information at the time, whole body physiological based pharmacoki-netics (PBPK) did not become of age until the 1960s, when, with the aid of the digital computer, modeling contributions from the chemical engineering community reawakened interest in this area. Since then, there have been numerous applications of the approach to a wide variety of chemical and drug substances, varying from small to large molecules, as well as investigations with environmental compounds. Compared, for example, to the sum of exponentials modeling, which is purely de-scriptive of the observed behavior of the substance under investigation, whole body PBPK modeling provides a mechanistic and more realistic description of the behav-ior of the substance in various tissues, with the intent of addressing such questions as: Why do we see the ob-served behavior? Can we explain differences among compounds? Can we better predict pharmacokinetics in human from in vitro and preclinical information and provide increasingly confident predictions of events oc-curring with drugs at target and other sites (which are rarely directly observable in humans), with age, in dis-ease, and when co-administered with other drugs.

Cation by industry and in regulatory submissions. Yet, there is an increasing impetus for the use of PBPK mod-eling within industry driven in part by the desire to make more efficient and informed selection of compounds for development from the myriad coming out of combinato-rial chemistry and high throughput biological screens, and in part from the general increasing acceptance of modeling in drug discovery and development as wit-nessed, for example, in the widening use in clinical trial design and simulation. Moreover, an increasing body of physiological, biological, and pharmacological data has become available over the years to inform PBPK model-ing. Collectively, these factors created the impetus for, and suggested the timeliness of, the workshop.