Computational Predictions of Nonclinical Pharmacokinetics at the Drug Design Stage.

Although computational predictions of pharmacokinetics (PK) are desirable at the drug design stage, existing approaches are often limited by prediction accuracy and human interpretability. Using a discovery data set of mouse and rat PK studies at Roche (9,685 unique compounds), we performed a proof-of-concept study to predict key PK properties from chemical structure alone, including plasma clearance (CLp), volume of distribution at steady-state (Vss), and oral bioavailability (F). Ten machine learning (ML) models were evaluated, including Single-Task, Multitask, and transfer learning approaches (i.e., pretraining with