ABSTRACT
This chapter provides an overview of the in silico approaches for estimating interindividual variability in partition coefficients (PC) for use in physiologically based pharmacokinetic (PBPK) modeling and risk assessment. The in silico approaches for estimating PCs are one of the three types: empirical, mechanistic, and semiempirical. The mechanistic and semiempirical methods are based on the biological and chemical properties that determine the PCs. Mechanistic and semiempirical in silico approaches, on the other hand, are based on properties that are specific to chemicals as well as characteristics that are specific to an individual or a population. The intraspecific or interindividual variability factor, reflecting the pharmacokinetic component, can be estimated either using measured data on biomarker concentrations collected in human studies or using pharmacokinetic models. The PBPK models facilitate the estimation of the magnitude of interindividual variation in tissue dose resulting from the interindividual variability in mechanistic determinants or input parameters, namely physiological parameters, PC, and metabolic constants.
