Modeling Interindividual Variation in Physiological Factors Used in PBPK Models of Humans

Abstract

Modeling interindividual variation in internal doses in humans using PBPK models requires data on the variation in physiological parameters across the population of interest. These data should also reflect the correlations between the values of the various parameters in a person. In this project, we develop a source of data for human physiological parameters where (1) the parameter values for an individual are correlated with one another, and (2) values of parameters capture interindividual variation in populations of a specific gender, race, and age range. The parameters investigated in this project include: (1) volumes of selected organs and tissues; (2) blood flows for the organs and tissues; and (3) the total cardiac output under resting conditions and average daily inhalation rate. These parameters are expressed as records of correlated values for the approximately 30,000 individuals evaluated in the NHANES III survey. A computer program, Physiological Parameters for PBPK Modeling (P3M), is developed that allows records to be retrieved randomly from the database with specification of constraints on age, sex, and ethnicity. P3M is publicly available. The database and accompanying software provide a convenient tool for parameterizating models of interindividual variation in human pharmacokinetics.