Reduction of quantitative systems pharmacology models using artificial neural networks.

Journal: Journal of pharmacokinetics and pharmacodynamics
PMID:

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.

Authors

  • Abdallah Derbalah
    School of Pharmacy, University of Otago, 18 Frederick St, North Dunedin, Dunedin, 9016, New Zealand. abdallah.derbalah@postgrad.otago.ac.nz.
  • Hesham S Al-Sallami
    School of Pharmacy, University of Otago, 18 Frederick St, North Dunedin, Dunedin, 9016, New Zealand.
  • Stephen B Duffull
    School of Pharmacy, University of Otago, 18 Frederick St, North Dunedin, Dunedin, 9016, New Zealand.