Pharmacokinetics and pharmacogenetics : bringing the magic bullet closer to reality

Abstract

Why do some patients respond positively to some drugs, while others may experience adverse effects? Can we predict which patients will react in which way? Does a magic bullet exist? The trend towards pharmacogenetics and personalised medicine in the last few years has somewhat sidelined the relevance of the traditional pharmaceutical sciences, such as pharmacokinetics and pharmacodynamics. Yet these actually are part and parcel of pharmacogenetics. Indeed understanding pharmacokinetics and pharmacodynamics in pharmacogenetics is essential in assessing the risk of new chemical entities (NCEs) in populations and individuals. Clinical pharmacokinetics, in fact, can be understood to have been a precursor to the implementation of pharmacogenetic understanding in the clinical setting. In this chapter, examples will be given of the strong interrelation between pharmacogenetics and the various pharmacokinetics processes i.e. absorption, distribution, metabolism and elimination. Reference will be made to studies which have shown how pharmacogenetics can be reinterpreted into pharmacokinetic principles, thus leading to the individualisation of drug therapy in the individual patient. The impact on recent regulatory guidelines published on the role of pharmacokinetics in pharmacogenetics and their impact on regulation of new medicinal drug development will also be discussed.