The intention of this chapter is to provide an overview of how pharmacokinetics, also termed PK, is applied in early drug development. While there are many readily available printed and web accessible sources on pharmacokinetics, its technical terms, model definitions, and calculation methods; how the science of pharmacokinetics is used in specific situations, namely early drug development are not as readily covered. In fact, the reader will see that the continual theme in this chapter is that a small amount of pharmacokinetic data and its interpretation in the first nonclinical or clinical study is important in obtaining additional pharmacokinetic, safety, and efficacy information for the next study. The role of PK in the three phases of clinical drug development is described as well as the types of early Phase 1 studies where PK determinations are important. The PK measurements in the first in humans study (FIH) provide a tentative confirmation of safety at the measured exposures from the tested dose levels. Even if exposures from a given dose change due to food-effects, drug–drug interaction, drug-disease interactions, or use in a special population, safety can be assessed by bridging these results to the initial safety or efficacy exposures.
Part of the book: Pharmacokinetics and Adverse Effects of Drugs