ADME Optimization in Drug Discovery

An acceptable human pharmacokinetic (PK) profile increases the probability of a promising candidate drug becoming a successful therapy. The development of a mechanistic understanding of the disposition of candidate drugs toward confident predictions of key properties associated with human drug absorption, metabolism, distribution, and excretion is critical. This is achievable from a consideration of physicochemical properties, data from in vitro assays with human-derived material and from in vivo animal studies. This article targets medicinal chemists and drug design teams and provides general definitions of fundamental PK parameters together with the best-practiced characterization, optimization, and prediction strategies employed in the authors' laboratory.