Role of Pharmacokinetics and Pharmacokinetic Modeling in Drug Development

Mechanistic understanding of drug absorption, distribution, metabolism and excretion (ADME) processes is critically important during the drug development process. Models of drug absorption, distribution and clearance via the liver or the kidneys have been developed with increasing complexity. These models, including physiologically based pharmacokinetic (PBPK) models can integrate mechanistic and physiological information of ADME concepts to predict drug disposition in patients. When coupled with solid understanding of fundamental pharmacokinetic principles and rigorously determined preclinical data, modeling and simulation allows translation and in silico prediction of plasma concentration time curves prior to first in human (FIH) studies. This chapter covers the fundamental ADME concepts in light of the drug development process and how ADME parameters may be incorporated into PBPK models to support drug development.