Adams Kimberly, Li Xinnong, Rohan Lisa, Bies Robert
School of Pharmacy and Pharmaceutical Sciences, State University of New York, Buffalo, NY, USA.
Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, USA.
Expert Opin Drug Metab Toxicol. 2025 Apr;21(4):429-444. doi: 10.1080/17425255.2025.2470794. Epub 2025 Feb 27.
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.
通过女性生殖道(FRT)进行药物递送因其在局部和全身治疗方面的潜力而受到越来越多的关注。基于生理的药代动力学(PBPK)模型为理解FRT内药物的吸收、分布、代谢和排泄(ADME)提供了一种机制方法,这对于优化阴道感染、避孕和激素治疗等疾病的治疗至关重要。
本综述全面分析了FRT的PBPK建模现状,重点关注其生理和解剖复杂性。本文回顾了现有的FRT PBPK模型,并讨论了在生殖组织中模拟药物渗透和ADME过程的挑战。确定了数据差距,包括组织特异性生理参数和药物渗透性。探讨了方法学进展以及影响FRT中药物处置的生物学因素,包括激素周期、个体间变异性和多囊卵巢综合征等疾病状态。
FRT的PBPK模型在改善药物递送和治疗个性化方面具有巨大潜力。然而,必须解决当前数据可用性和模型验证方面的局限性。未来整合真实世界患者数据、先进成像技术和药效学建模的研究将提高这些模型的准确性和临床实用性,推动药物开发和监管进程。