Model-based Strategies of Drug Dosing for Pharmacokinetic Systems

PAULINE THEMANS, Flora Tshinanu Shinanu Musuamba, Joseph WINKIN

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Abstract

The aim of this paper is to report analytical and individual-based methods for antibiotic dose selection, that are based on tools from system and control theory. A brief system analysis of standard population pharmacokinetic models proves that such models are nonnegative and stable. Then, an input-output analysis leads to an open-loop control law which yields a dosing for the “average” patient, based on the equilibrium trajectory of the system. This approach is then incorporated into a “worst-case” analysis based on the monotony of the state trajectories with respect to the clearance (model parameter). Finally, an heuristic method of an estimated state feedback is presented. Thanks to numerical simulations, these methods were successively illustrated on a model describing the pharmacokinetic of meropenem, an intravenous antibiotic for treatment of severe sepsis.
Original languageEnglish
Pages (from-to)16061-16068
Number of pages8
JournalIFAC-PapersOnLine
Volume53
Issue number2
Early online date14 Apr 2021
DOIs
Publication statusE-pub ahead of print - 14 Apr 2021

Keywords

  • Pharmacokinetic systems
  • monotone systems
  • variability
  • drug dosing
  • asymptotic analysis
  • worst-case design
  • state estimation
  • state feedback

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