Computing optimal drug dosing with OptiDose: implementation in NONMEM

Freya Bachmann; Gilbert Koch; Robert J Bauer; Britta Steffens; Gabor Szinnai; Marc Pfister; Johannes Schropp

doi:10.1007/s10928-022-09840-w

Computing optimal drug dosing with OptiDose: implementation in NONMEM

J Pharmacokinet Pharmacodyn. 2023 Jun;50(3):173-188. doi: 10.1007/s10928-022-09840-w. Epub 2023 Jan 27.

Authors

Freya Bachmann¹, Gilbert Koch², Robert J Bauer³, Britta Steffens⁴, Gabor Szinnai^{5

6}, Marc Pfister^{4

6}, Johannes Schropp¹

Affiliations

¹ Department of Mathematics and Statistics, University of Konstanz, PO Box 195, 78457, Konstanz, Germany.
² Pediatric Pharmacology and Pharmacometrics, University of Basel Children's Hospital, Spitalstrasse 33, 4056, Basel, Switzerland. [email protected].
³ ICON Clinical Research LLC, Blue Bell, PA, USA.
⁴ Pediatric Pharmacology and Pharmacometrics, University of Basel Children's Hospital, Spitalstrasse 33, 4056, Basel, Switzerland.
⁵ Pediatric Endocrinology and Diabetology, University of Basel Children's Hospital, Spitalstrasse 33, 4056, Basel, Switzerland.
⁶ Department of Clinical Research, University of Basel and University Hospital Basel, Basel, Switzerland.

PMID: 36707456
DOI: 10.1007/s10928-022-09840-w

Abstract

Determining a drug dosing recommendation with a PKPD model can be a laborious and complex task. Recently, an optimal dosing algorithm (OptiDose) was developed to compute the optimal doses for any pharmacometrics/PKPD model for a given dosing scenario. In the present work, we reformulate the underlying optimal control problem and elaborate how to solve it with standard commands in the software NONMEM. To demonstrate the potential of the OptiDose implementation in NONMEM, four relevant but substantially different optimal dosing tasks are solved. In addition, the impact of different dosing scenarios as well as the choice of the therapeutic goal on the computed optimal doses are discussed.

Keywords: Dose optimization; Optimal control; Optimal dosing; Pharmacometrics; Therapeutic goal.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Algorithms*
Software*