A methodology for solving physiologically based pharmacokinetic models without the use of simulation softwares

Area of Science:

• Pharmacokinetics
• Computational Biology
• Toxicology

Background:

• Physiologically based pharmacokinetic (PBPK) models are crucial for understanding chemical disposition in biological systems.
• Traditional PBPK modeling often relies on specialized, proprietary simulation software, posing accessibility and transparency challenges.
• Developing user-friendly, accessible methods for PBPK model analysis is essential for broader scientific application.

Purpose of the Study:

• To develop and validate a methodology for solving PBPK models without commercial simulation software.
• To demonstrate the application of this methodology using Microsoft Excel and Euler's method.
• To provide an accessible tool for understanding and solving PBPK models.

Main Methods:

• Parameter values and model equations were implemented in Microsoft Excel spreadsheets.
• Numerical integration was performed using Euler's method within Excel.
• The methodology was applied to simulate styrene pharmacokinetics in rats and validated against commercial software (ACSL).

Main Results:

• The Excel-based methodology successfully simulated styrene pharmacokinetics in rats.
• Simulation results obtained using Excel and ACSL differed by less than 1%.
• Graphical representation of simulation data was readily achieved using Excel's built-in features.

Conclusions:

• A validated, accessible methodology for solving PBPK models using Microsoft Excel has been developed.
• This approach offers a transparent alternative to "black-box" simulation software, enhancing understanding.
• The method facilitates the application of PBPK modeling by researchers without access to specialized software.