Introduction of an artificial neural network–based method for concentration‐time predictions

Abstract

Pharmacometrics and the application of population pharmacokinetic (PK) modeling play a crucial role in clinical pharmacology. These methods, which describe data with well-defined equations and estimate physiologically interpretable parameters, have not changed substantially during the past decades. Although the methods have proven their usefulness, they are often resource intensive and require a high level of expertise. We investigated whether a method based on artificial neural networks (ANNs) may provide an alternative approach for the prediction of concentration-time curve to supplement the gold standard methods. In this work, we used simulated data to overcome the requirement for a large clinical training data set, implemented a pharmacologically reasonable network architecture to improve extrapolation to different dosing schemes, and used transfer learning to quickly adapt the predictions to new patient groups. We demonstrate that ANNs are able to learn the shape of concentration-time curves and make individual predictions based on a short sequence of PK measurements. Furthermore, an ANN trained on simulated data was applied to real clinical data and was demonstrated to extrapolate to different dosing schemes. We also adapted the ANN trained on simulated healthy subjects to simulated hepatic impaired patients through transfer learning. In summary, we demonstrate how ANNs could be leveraged in a PK workflow to efficiently make individual concentration-time predictions, and we discuss the current limitations and advantages of such an ANN-based method.

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