CHAPTER 8. Prediction of Human Pharmacokinetics, Exposure and Therapeutic Dose in Drug Discovery

Based on a robust understanding of how physicochemical properties drive PK, relatively little experimental data is required establish a drug discovery optimisation strategy and gain confidence that clinical candidates are selected with a high likelihood of achieving an acceptable clinical PK profile. This chapter is designed to be used by the practicing medicinal chemist and attempts to provide both the context and some specific advice to apply best practice for PK and efficacious dose prediction. Hints and tips are suggested throughout the chapter and methods to predict human PK parameters outlined. Worked examples of both proprietary candidate and approved drugs are used to highlight particular themes. This chapter can be used in conjunction with the associated Dose to Man iPad app which allows medicinal chemists to simulate therapeutic doses and exposures in Man for their drug discovery projects via the approaches and equations presented herein. ‘Dose to man’ approach integrates information to rank and select compounds, which as a minimum, is a sophisticated scoring function, and at best, is an effective tool for assessing clinical utility.