Model-based Strategies of Drug Dosing for Pharmacokinetic Systems

PAULINE THEMANS, Flora Tshinanu Shinanu Musuamba, Joseph WINKIN

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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.
langue originaleAnglais
Pages (de - à)16061-16068
Nombre de pages8
Numéro de publication2
Date de mise en ligne précoce14 avr. 2021
Les DOIs
Etat de la publicationE-pub ahead of print - 14 avr. 2021

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