Pharmacokinetic Tools and Applications

Abstract

Drug toxicity, as well as therapeutic activity, is contingent upon the parent drug, or a derivative thereof, reaching the relevant site of action in the body, at sufficient concentration, over a given period of time. Thus, the potential to truly elicit an effect is governed by both the intrinsic activity/toxicity of the drug (or its transformation products) and its pharmacokinetic profile. As the pharmaceutical industry has become increasingly aware of the role of pharmacokinetics in determining drug activity and toxicity, the range of software, both freely available and commercial, to predict relevant properties has proliferated. Such tools can be considered on three different levels, applicable at different stages within the drug development process and providing increasing detail and relevance of information. Level (i) is the prediction of fundamental physicochemical properties that can be used to screen vast virtual libraries of potential candidates. Level (ii), predicting the individual absorption, distribution, metabolism, and excretion (ADME) characteristics of potential drugs, can also be applied to many compounds simultaneously. Level (iii), predicting the concentration-time profile of a drug in blood or specific tissues/organs for individuals or a population, is the most sophisticated level of prediction, applied to fewer candidates. In this chapter, in silico tools for predicting ADME-relevant properties, across these three levels, and the applications of this information, are described using exemplar, freely available resources. Further resources are signposted but not all are considered in detail as the purpose here is more to provide an introduction to the capabilities and practicalities of the tools, rather than to provide an exhaustive review of all the tools available.

Keywords: ADME modeling; ADME webtools; PBPK tools; QSAR; SAR.