Computing optimal drug dosing regarding efficacy and safety: the enhanced OptiDose method in NONMEM

Recently, an optimal dosing algorithm (OptiDose) was developed to compute the optimal drug doses for any pharmacometrics model for a given dosing scenario. In the present work, we enhance the OptiDose concept to compute optimal drug dosing with respect to both efficacy and safety targets. Usually, these are not of equal importance, but one is a top priority, that needs to be satisfied, whereas the other is a secondary target and should be achieved as good as possible without failing the top priority target. Mathematically, this leads to state-constrained optimal control problems. In this paper, we elaborate how to set up such problems and transform them into classical unconstrained optimal control problems which can be solved in NONMEM. Three different optimal dosing tasks illustrate the impact of the proposed enhanced OptiDose method.

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Publication Details

Journal
Journal of Pharmacokinetics and Pharmacodynamics
Published
2024-10-08
DOI
https://doi.org/10.1007/s10928-024-09940-9
Citations
3
Primary Topic
Antibiotics Pharmacokinetics and Efficacy
Type
article
Field-Weighted Citation Impact
1.34

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article

Computing optimal drug dosing regarding efficacy and safety: the enhanced OptiDose method in NONMEM

Gilbert Koch, Marc Pfister, Britta Steffens, Johannes Schropp et al.
3 citations
Journal of Pharmacokinetics and Pharmacodynamics
Antibiotics Pharmacokinetics and Efficacy
1.34
article

Computing optimal drug dosing regarding efficacy and safety: the enhanced OptiDose method in NONMEM

Gilbert Koch, Marc Pfister, Britta Steffens, Johannes Schropp, Gabor Szinnai, Robert J. Bauer, Freya Bachmann
article en
3 citations

Abstract

Recently, an optimal dosing algorithm (OptiDose) was developed to compute the optimal drug doses for any pharmacometrics model for a given dosing scenario. In the present work, we enhance the OptiDose concept to compute optimal drug dosing with respect to both efficacy and safety targets. Usually, these are not of equal importance, but one is a top priority, that needs to be satisfied, whereas the other is a secondary target and should be achieved as good as possible without failing the top priority target. Mathematically, this leads to state-constrained optimal control problems. In this paper, we elaborate how to set up such problems and transform them into classical unconstrained optimal control problems which can be solved in NONMEM. Three different optimal dosing tasks illustrate the impact of the proposed enhanced OptiDose method.

Journal of Pharmacokinetics and PharmacodynamicsVol. 51(6)
University of Basel (CH), University of Konstanz (DE), University Hospital of Basel (CH), Pinnacle Clinical Research (US), University Children’s Hospital Basel (CH)
National Science Foundation, Deutsche Forschungsgemeinschaft, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Universität Konstanz, Botnar Research Centre for Child Health, University of Basel
Good health and well-being
Openalex Percentile: Top 18%
Antibiotics Pharmacokinetics and Efficacy
1.34
DOIOpen Access PDFOpenAlex
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