Optimizing dose regimens and fixed dose combination ratios in clinical trials.

Area of Science:

• Pharmacology
• Computational Biology
• Drug Development

Background:

• Therapeutic drug treatment relies on maintaining optimal blood concentrations.
• Suboptimal drug levels can reduce efficacy and increase toxicity.
• Current dose-finding methods often rely on simulation-based approaches.

Purpose of the Study:

• To develop a novel computer-assisted method for optimizing drug dose regimens.
• To establish a general theory and computational criteria for optimal dose regimens.
• To identify optimal combination ratios for fixed-dose drug combinations.

Main Methods:

• Explicit optimization of a target criterion for dose regimen calculation.
• Development of a general theory for dose regimens.
• Algorithm adaptation for restricting drug concentration profiles within a therapeutic range.

Main Results:

• A novel method for computer-assisted dose finding has been developed.
• The proposed method optimizes dose regimens by explicitly targeting therapeutic concentration criteria.
• The algorithm can simultaneously determine optimal dose regimens and combination ratios for fixed-dose combinations.

Conclusions:

• This optimization approach offers a more efficient alternative to simulation-based methods.
• The methodology is applicable to single drugs and fixed-dose combinations, particularly in anti-infectives.
• Potential applications include randomized concentration-controlled trials requiring strict adherence to target concentrations.