Approaches Towards Prediction of CNS PK and PD

It has to be realized that a drug’s pharmacokinetics and pharmacodynamics results from the combination of drug properties and biological system characteristics. This chapter will address the gross anatomy and physiology of the central nervous system (CNS) and how physiological processes play a role in CNS drug-target site distribution. This is followed by physiologically based pharmacokinetic (PBPK) model characteristics and the recently developed multi-CNS compartment PBPK models for small molecules and antibodies, with good predictive power for CNS target site distribution in human, as it explicitly distinguishes between drug and systems properties. Understanding the CNS target site concentrations (Stevens et al. 2012) further helps in the development of (PB)PK-pharmacodynamic (PD) models in healthy and disease conditions to further pave the way to predict the right drug at the right location, right time, and right concentration (De Lange 2013a, b).