Current Status in PBPK Modeling

Physiologically based pharmacokinetic (PBPK) modeling is a mathematical approach that integrates the intrinsic pharmacokinetic properties of a drug and the physiological parameters of a target population. It has been utilized in a wide range of applications, from the early stages of drug discovery to the submission to regulatory authorities. In this chapter, we aimed to evaluate the accuracy of the PBPK models in predicting PK parameters related to drug absorption, distribution, metabolism, and excretion, as well as the plasma concentration–time profiles under various clinical scenarios including the effect of food, drug–drug interactions, hepatic or renal impairment, and pediatric growth processes. A survey of the recent literature revealed that, although the predicted values of area under the plasma concentration–time curve in each report were often claimed to be within twofold of the observed values, the following issues were found: (i) the method of model construction is not clearly described in the literature and (ii) the method of parameter optimization is not standardized among the literature. In order to increase the reliability of PK predictions by PBPK models, standardization of the model construction processes is desirable.