PBPK models of the female reproductive tract: current and future analysis

Drug delivery via the female reproductive tract (FRT) has garnered increasing attention due to its potential for local and systemic therapies. Physiologically Based Pharmacokinetic (PBPK) models offer a mechanistic approach to understanding drug absorption, distribution, metabolism, and excretion (ADME) within the FRT, which is critical for optimizing treatments for conditions such as vaginal infections, contraception, and hormonal therapies.

This review provides a comprehensive analysis of the current state of PBPK modeling for the FRT, focusing on its physiological and anatomical complexities. The paper reviews existing FRT PBPK models and discusses the challenges of simulating drug permeation and ADME processes in reproductive tissues. Data gaps, including tissue-specific physiological parameters and drug permeability, are identified. Methodological advances and biological factors influencing drug disposition in the FRT are explored, including hormonal cycles, interindividual variability, and disease states like polycystic ovary syndrome.

PBPK models for the FRT hold significant promise for improving drug delivery and therapy personalization. However, current limitations in data availability and model validation must be addressed. Future research integrating real-world patient data, advanced imaging techniques, and pharmacodynamic modeling will enhance these models' accuracy and clinical utility, advancing drug development and regulatory processes.