Reduction of quantitative systems pharmacology models using artificial neural networks

J Pharmacokinet Pharmacodyn. 2021 Aug;48(4):509-523. doi: 10.1007/s10928-021-09742-3. Epub 2021 Mar 2.

Abstract

Quantitative systems pharmacology models are often highly complex and not amenable to further simulation and/or estimation analyses. Model-order reduction can be used to derive a mechanistically sound yet simpler model of the desired input-output relationship. In this study, we explore the use of artificial neural networks for approximating an input-output relationship within highly dimensional systems models. We illustrate this approach using a model of blood coagulation. The model consists of two components linked together through a highly dimensional discontinuous interface, which creates a difficulty for model reduction techniques. The proposed approach enables the development of an efficient approximation to complex models with the desired level of accuracy. The technique is applicable to a wide variety of models and provides substantial speed boost for use of such models in simulation and control purposes.

Keywords: Machine learning; Model-order reduction; Neural networks; Quantitative systems pharmacology.

MeSH terms

  • Anticoagulants / pharmacology
  • Blood Coagulation / drug effects
  • Dose-Response Relationship, Drug
  • Humans
  • International Normalized Ratio
  • Models, Statistical*
  • Neural Networks, Computer*
  • Pharmacology / methods*
  • Systems Biology

Substances

  • Anticoagulants