基于生理的口服吸收模型在仿制药研发中的应用和趋势

建立良好的体内外相关性有助于准确分辨出仿制药与参比制剂在有效性、质量、稳定性和安全性相关的药学差异，这对于仿制药的开发意义重大。与传统的房室模型反卷积法相比，基于生理的口服吸收模型可从口服吸收药时曲线中分离出渗透、代谢或转运的动力学过程，从而更为准确地描述体内吸收曲线，更好地建立起体内外相关性。目前，基于生理的口服吸收模型已被欧美制药企业普遍用于剂型开发和生物等效性试验的支持，并被FDA推荐为促进仿制药开发的主要工具之一。本文综述了基于生理的口服吸收模型的应用进展、研究策略和面临的挑战与希望，以期支持我国目前正在开展的仿制药研发和一致性评价工作。

Application and progress of physiologically-based oral absorption model in clinical development of generic drugs

Demonstration of in vitro in vivo correlation (IVIVC) could identify key factors of pharmaceutical characteristics affecting drug efficacy, quality, stability, and safety. Compared with compartmental model-based deconvolution method, physiologically-based oral absorption model could better establish IVIVC by separating kinetics of permeability, metabolism, and transportation. Currently, physiologically-based oral absorption model has been extensively employed by big pharmaceutical companies in US and Europe to develop new formulation and support clinical bioequivalence (BE) trials. It is one of the major tools to simplify development of generic drugs and to evaluate the quality of generic drug application utilized by Food and Drug Administrator (FDA) in US. Regarding the regulatory need of Abbrevitive New Drug Application (ANDA) and generic drug consistency evaluation in China, we reviewed the application progress, investigation strategy, challenges, and regulatory utility of physiologically-based oral absorption model to support generic drug development in China.