Zhang Cindy X, Arnold Samuel L M
Department of Pharmaceutics, University of Washington, Seattle, Washington.
Department of Pharmaceutics, University of Washington, Seattle, Washington.
Drug Metab Dispos. 2025 Jan;53(1):100014. doi: 10.1124/dmd.122.000964. Epub 2024 Nov 22.
Physiologically based pharmacokinetic (PBPK) modeling is a physiologically relevant approach that integrates drug-specific and system parameters to generate pharmacokinetic predictions for target populations. It has gained immense popularity for drug-drug interaction, organ impairment, and special population studies over the past 2 decades. However, an application of PBPK modeling with great potential remains rather overlooked-prediction of diarrheal disease impact on oral drug pharmacokinetics. Oral drug absorption is a complex process involving the interplay between physicochemical characteristics of the drug and physiological conditions in the gastrointestinal tract. Diarrhea, a condition common to numerous diseases impacting many worldwide, is associated with physiological changes in many processes critical to oral drug absorption. In this Minireview, we outline key processes governing oral drug absorption, provide a high-level overview of key parameters for modeling oral drug absorption in PBPK models, examine how diarrheal diseases may impact these processes based on literature findings, illustrate the clinical relevance of diarrheal disease impact on oral drug absorption, and discuss the potential and challenges of applying PBPK modeling in predicting disease impacts. SIGNIFICANCE STATEMENT: Pathophysiological changes resulting from diarrheal diseases can alter important factors governing oral drug absorption, contributing to suboptimal drug exposure and treatment failure. Physiologically based pharmacokinetic (PBPK) modeling is an in silico approach that has been increasingly adopted for drug-drug interaction potential, organ impairment, and special population assessment. This Minireview highlights the potential and challenges of using physiologically based pharmacokinetic modeling as a tool to improve our understanding of how diarrheal diseases impact oral drug pharmacokinetics.
基于生理的药代动力学（PBPK）建模是一种与生理相关的方法，它整合了药物特异性参数和系统参数，以生成针对目标人群的药代动力学预测。在过去20年中，它在药物相互作用、器官损伤和特殊人群研究方面广受欢迎。然而，PBPK建模在一个具有巨大潜力的应用方面仍被相当忽视——预测腹泻疾病对口服药物药代动力学的影响。口服药物吸收是一个复杂的过程，涉及药物的物理化学特性与胃肠道生理状况之间的相互作用。腹泻是许多影响全球众多人的疾病所共有的一种状况，它与口服药物吸收的许多关键过程中的生理变化有关。在本综述中，我们概述了控制口服药物吸收的关键过程，对PBPK模型中口服药物吸收建模的关键参数进行了高层次概述，根据文献研究结果探讨腹泻疾病可能如何影响这些过程，阐述腹泻疾病对口服药物吸收影响的临床相关性，并讨论应用PBPK建模预测疾病影响的潜力和挑战。重要声明：腹泻疾病引起的病理生理变化可改变控制口服药物吸收的重要因素，导致药物暴露不理想和治疗失败。基于生理的药代动力学（PBPK）建模是一种计算机模拟方法，已越来越多地用于药物相互作用潜力、器官损伤和特殊人群评估。本综述强调了使用基于生理的药代动力学建模作为工具来增进我们对腹泻疾病如何影响口服药物药代动力学的理解的潜力和挑战。
