基于生理的口服吸收模型在仿制药研发中的应用和趋势

中国临床药理学与治疗学 ›› 2017, Vol. 22 ›› Issue (9): 961-965.

• 专论 • 下一篇

基于生理的口服吸收模型在仿制药研发中的应用和趋势

李丽，杨进波

国家食品药品监督管理总局药品审评中心，北京 100038

收稿日期:2017-07-25 修回日期:2017-08-03 出版日期:2017-09-26 发布日期:2017-09-30
作者简介:李丽，药理学硕士，国家食品药品监督管理总局药品审评中心统计与临床药理学部审评员。2006年毕业于中国医学科学院中国协和医科大学北京协和医院，临床药理学专业。毕业后从事药物临床试验机构的管理工作，以及临床药学工作。2013年加入药审中心，承担临床药理学及生物等效性试验审评工作。主要工作和学习经历包括临床前药代研究、I-IV期药物临床试验、BE试验、生物样品分析、临床药理学在新药研发中的应用、定量药理学研究、临床药学相关工作、仿制药BE审评工作等。主要承担主笔起草多个药物研发技术指导原则和规范。 Tel：010-68921532 E-mail：lil@cde.org.cn 杨进波，医学博士，国家食品药品监督管理总局药品审评中心统计与临床药理学部部长。于2003年作为一名临床审评员加入药审中心，先后参与审评的品种涉及抗肿瘤药物、神经疾病药物、精神疾病药物、内分泌和代谢疾病药物、呼吸道和过敏性疾病药物、抗感染药物、抗病毒药物、皮肤疾病药物、生殖泌尿药物等多个疾病领域。现发表中英文论文近百篇，主持并参加了多个药物研发指导原则和规范的撰写工作，参与多部专业论著编写、翻译、审校。 Tel：010-68921400 E-mail：yangjb@cde.org.cn

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

LILi, YANG Jinbo

Center for Drug Evaluation, China Food and Drug Administration, Beijing 100038, China

Received:2017-07-25 Revised:2017-08-03 Online:2017-09-26 Published:2017-09-30

摘要/Abstract

摘要：

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。

关键词: 基于生理的口服吸收模型, 仿制药

Abstract:

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.

Key words: physiologically-based oral absorption model, generic drugs

中图分类号:

R969.1

李丽，杨进波. 基于生理的口服吸收模型在仿制药研发中的应用和趋势[J]. 中国临床药理学与治疗学, 2017, 22(9): 961-965.

LILi, YANG Jinbo. Application and progress of physiologically-based oral absorption model in clinical development of generic drugs[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2017, 22(9): 961-965.

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基于生理的口服吸收模型在仿制药研发中的应用和趋势

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

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