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Sex-Related Differences in Physiologically-Based Biopharmaceutics Modeling
Marianela Chavarría-Rojas1,2,3, Mub Murshed4, Marianela Lorier1
1Department of Pharmaceutical Sciences, Faculty of Chemistry, Universidad de la República, Montevideo, Uruguay.
CPT: Pharmacometrics & Systems Pharmacology
|July 30, 2026
Summary
Physiologically based pharmacokinetic (PBPK) and biopharmaceutics (PBBM) models often lack sex-specific gastrointestinal data, impacting drug development predictions. Refining these parameters improves model accuracy for virtual female populations.
Area of Science:
- Pharmacokinetics and Biopharmaceutics
- Computational Drug Development
- Sex-Based Drug Response
Background:
- Physiologically based pharmacokinetic (PBPK) and physiologically-based biopharmaceutics (PBBM) modeling are crucial for predicting drug absorption and disposition.
- Existing PBPK platforms often neglect sex-related differences in gastrointestinal physiology, potentially limiting prediction accuracy in virtual populations.
Purpose of the Study:
- To evaluate the incorporation of sex-related physiological differences in common PBPK platforms.
- To demonstrate the impact of these differences on pharmacokinetic predictions using ketoprofen as a case study.
Main Methods:
- Systematic review of three PBPK platforms for predefined sex-specific gastrointestinal parameters.
- Development and verification of three ketoprofen PBBM models in males.
- Extrapolation of models to females using default and refined sex-specific gastrointestinal parameters.
Main Results:
- All reviewed PBPK platforms included general sex-related anatomical and physiological differences but lacked specific gastrointestinal tract parameters.
- Default female settings in PBBM models led to overpredicted Cmax and underestimated Tmax, diminishing observed sex differences.
- Refining gastrointestinal tract parameters for the female population significantly improved prediction performance and better reflected sex-specific pharmacokinetic differences.
Conclusions:
- Current PBPK platforms necessitate user-defined adjustments to accurately represent sex-specific gastrointestinal physiology.
- Incorporating detailed sex-specific gastrointestinal parameters enhances the representativeness and accuracy of PBBM applications in drug development.
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