BioDMET: a physiologically based pharmacokinetic simulation tool for assessing proposed solutions to complex...

Area of Science:

• Pharmacokinetics and Pharmaceutical Sciences
• Computational Biology and Bioinformatics
• Biomedical Engineering

Background:

• Physiologically based pharmacokinetic (PBPK) models are essential for predicting drug behavior in vivo.
• Existing PBPK models often lack the anatomical detail and flexibility required for complex applications like imaging agent development.
• There is a need for accessible, mechanistic PBPK software to accelerate drug and imaging agent development.

Purpose of the Study:

• To develop a detailed, whole-body PBPK modeling tool (BioDMET) for simulating pharmaceutical agent distribution.
• To create a flexible and user-friendly PBPK software that can be adapted to diverse research problems.
• To facilitate the broad adoption of PBPK modeling in drug discovery and development.

Main Methods:

• Developed a whole-body PBPK model incorporating detailed anatomy, fluid circulation (arterial, venous, lymph), and cellular-level transport and biotransformation.
• Utilized ordinary differential equations (ODEs) to represent physiological processes at macroscopic and molecular scales.
• Implemented features for dynamic compartment collapsing to adjust model complexity and integrated with physics-based image simulators.

Main Results:

• BioDMET accurately models the distribution of pharmaceutical agents in human and animal tissues over time.
• The model has been successfully applied to imaging feasibility studies in oncology, neurology, cardiology, and diabetes.
• Demonstrated adaptability for antimicrobial therapeutic development and analysis of pharmacodynamic/pharmacokinetic variations.

Conclusions:

• BioDMET provides a robust, adaptable, and user-friendly platform for PBPK modeling in drug and imaging agent development.
• The software's flexibility allows for the study of diverse pharmacokinetic/pharmacodynamic problems, including inter-individual differences and disease states.
• By offering a free, mechanistic tool with ready-to-use data, BioDMET aims to accelerate PBPK modeling adoption in the scientific community.