Pharmacokinetic Data Analysis and Modeling of ADME Processes

The PK of unchanged drug and the pseudo-PK parameters of total radioactivity (TRA) must be estimated in human ADME studies. With multiple PK samples collected in plasma and excreta, the PK parameters that represent the extent of a drug in or clearance from the circulation system are readily determined using a noncompartment approach that can be executed quickly in routine and traditional PK data analysis without assumption on disposition of drug in the body. Mechanism- or compartment-based PK models contain specific expression to characterize, in a quantitative manner, processes on the causal path from absorption, distribution, and metabolism to elimination. Data analysis using modeling will provide information on not only the extent of a drug in the body but also the rate of a drug transferring through different parts of the body. Pooling PK data from a human ADME together with the data from the other studies of the same molecule can help scientists build a more robust population PK model, which can be used in interpreting or predicting the underlying physiological or pathological processes that drugs act on and for optimizing therapy with drugs that have a complex disposition. Keywords: pharmacokinetics; absorption kinetics; distribution kinetics; metabolism kinetics; elimination kinetics; mass balance; radioactivity; noncompartmental analysis; compartmental analysis