Structure – ADME relationship: still a long way to go?

Background: Theoretical models for predicting absorption, distribution, metabolism and excretion (ADME) properties play increasingly important roles in support of the drug development process. Objective: We briefly review the in silico prediction models for three important ADME properties, namely, aqueous solubility, human intestinal absorption, and oral bioavailability. Methods: Rather than giving detailed descriptions of the ADME prediction models, we focus on the discussions of the prediction accuracies of the in silico models. Results/conclusion: We find that the robustness and predictive capability of the ADME models are directly associated with the complexity of the ADME property. For the ADME properties involving complex phenomena, such as bioavailability, the in silico models usually cannot give satisfactory predictions. Moreover, the lack of large and high-quality data sets also greatly hinder the reliability of ADME predictions. While considerable progress has been achieved in ADME predictions, many challenges remain to be overcome.