Integrating machine learning with pharmacokinetic models: Benefits of scientific machine learning in adding neural networks components to existing PK models

Abstract

AbstractRecently, the use of machine‐learning (ML) models for pharmacokinetic (PK) modeling has grown significantly. Although most of the current approaches use ML techniques as black boxes, there are only a few that have proposed interpretable architectures which integrate mechanistic knowledge. In this work, we use as the test case a one‐compartment PK model using a scientific machine learning (SciML) framework and consider learning an unknown absorption using neural networks, while simultaneously estimating other parameters of drug distribution and elimination. We generate simulated data with different sampling strategies to show that our model can accurately predict concentrations in extrapolation tasks, including new dosing regimens with different sparsity levels, and produce reliable forecasts even for new patients. By using a scenario of fitting PK data with complex absorption, we demonstrate that including known physiological structure into an SciML model allows us to obtain highly accurate predictions while preserving the interpretability of classical compartmental models.