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

Area of Science:

• Pharmacometrics
• Optimal Control Theory
• Drug Dosing Optimization

Background:

• An optimal dosing algorithm (OptiDose) was previously developed for pharmacometric models.
• Current methods may not adequately balance competing efficacy and safety targets.

Purpose of the Study:

• To enhance the OptiDose algorithm for optimizing drug dosing considering both efficacy and safety.
• To address state-constrained optimal control problems arising from prioritized targets.

Main Methods:

• Formulating drug dosing optimization as a state-constrained optimal control problem.
• Transforming these problems into classical unconstrained optimal control problems.
• Utilizing the NONMEM software for solving the transformed problems.

Main Results:

• Demonstrated the successful enhancement of the OptiDose concept.
• Showcased the method's applicability through three distinct optimal dosing scenarios.
• Validated the approach for balancing prioritized efficacy and safety targets.

Conclusions:

• The enhanced OptiDose method effectively computes optimal drug doses considering prioritized efficacy and safety.
• This approach provides a robust framework for solving complex dosing optimization problems in pharmacometrics.
• The method facilitates improved therapeutic outcomes by balancing critical patient-specific targets.