Development and application of a PBPK modeling strategy to support antimalarial drug development

Area of Science:

• Pharmacokinetics
• Drug Development
• Malaria Research

Background:

• Physiologically-based pharmacokinetic (PBPK) models are crucial tools in drug development.
• Antimalarial drug development requires robust pharmacokinetic data for efficacy and safety.
• A collaborative effort was undertaken to develop PBPK models for antimalarials.

Purpose of the Study:

• To develop and validate PBPK models for 20 antimalarial drugs.
• To demonstrate the practical application and evolving strategy for using PBPK models in antimalarial drug development.
• To provide a shared resource of PBPK models and case studies for the global health research community.

Main Methods:

• Development of PBPK models using in vitro assay data and literature-based clinical studies.
• Application of PBPK models within the antimalarial drug development pipeline at Medicines for Malaria Venture (MMV).
• Analysis of drug-drug interaction liability for antimalarial combination therapies.

Main Results:

• Successfully developed PBPK models for 20 antimalarials, available to researchers.
• Demonstrated over five years of impactful application of these models in antimalarial drug development at MMV.
• Case studies showcase real-world applications in development and clinical decision-making, including drug interaction assessments.

Conclusions:

• PBPK modeling significantly benefits antimalarial drug development and decision-making processes.
• A strategic approach for integrating PBPK modeling into research and development has been established.
• The developed PBPK models and associated information serve as a valuable repository for global health research.