Application of machine learning techniques to the analysis and prediction of drug pharmacokinetics

In this review, we describe the current status and challenges in applying machine-learning techniques to the analysis and prediction of pharmacokinetic data. The theory of pharmacokinetics has been developed over decades on the basis of physiology and reaction kinetics. Mathematical models allow the reduction of pharmacokinetic data to parameter values, giving insight and understanding into ADME processes and predicting the outcome of different dosing scenarios. However, much information hidden in the data is lost through conceptual simplification with models. It is difficult to use mechanistic models alone to predict diverse pharmacokinetic time profiles, including inter-drug and inter-individual differences, in a cross-sectional manner. Machine learning is a prediction platform that can handle complex phenomena through data-driven analysis. As a resule, machine learning has been successfully adopted in various fields, including image recognition and language processing, and has been used for over two decades in pharmacokinetic research, primarily in the area of quantitative structure-activity relationships for pharmacokinetic parameters. Machine-learning models are generally known to provide better predictive performance than conventional linear models. Owing to the recent success in deep learning, models with new structures are being consistently proposed. These models include transfer learning and generative adversarial networks, which contribute to the effective use of a limited amount of data by diverting existing similar models or generating pseudo-data. How to make such newly emerging machine learning technologies applicable to meet challenges in the pharmacokinetics/pharmacodynamics field is now the key issue.