DEVELOPMENT OF PARTITION-COEFFICIENTS, V-MAX AND K-M VALUES, AND ALLOMETRIC RELATIONSHIPS

A knowledge of the methods used to obtain partition coefficients, V-max, and K-m values, and the use of allometric relationships is essential to understanding their role in physiologically based pharmacokinetic (PBPK) models. Vial equilibration methods for obtaining the partition coefficients of volatile and nonvolatile compounds were presented using the results from studies with p-chlorobenzotrifluoride (PCBTF) and isofenphos, respectively. Partition coefficients for volatile and nonvolatile compounds from published studies were included. Several published in vivo inhalation (gas uptake) studies and in vitro enzyme studies were presented to demonstrate several methods for obtaining V-max and K-m values. Allometric equations used in PBPK models for body weight scaling of respiration and cardiac rates between species were presented along with equations for within species body weight scaling of V-max.