Predicting the volume of distribution of drugs in humans

Recent studies have shown that many promising new drug candidates were abandoned due to poor pharmacokinetic properties (PKs). Therefore, it is important to predict the PKs of compounds during the early stages of drug development. The volume of distribution (VD) is one of the most important PK parameters. When considered along with systemic clearance, the VD determines the biological half-life, which is used for designing suitable dosage regimens and rational formulations. At present, the methods used to predict VD include (i) the extrapolation of animal data, (ii) physiologically based pharmacokinetic (PBPK) modeling and (iii) in silico approaches that employ quantitative structure-pharmacokinetic relationships (QSPR). In this article, the latest progress in the field of VD prediction is summarized in terms of the above three areas, respectively, and these approaches are expected to be valuable for screening new drugs during the early stages of drug discovery and development.