药动学–药效学模型在新药评价中的应用.PDFVIP

Drug Evaluation Research 第 34 卷 第 3 期 2011 年 6 月 - 161 - • 专 论 • 药动学 –药效学模型在新药评价中的应用 庄露凝 1, 2, 3 ，谷 元 1, 2 ，刘昌孝2* 1. 天津大学 化工学院，天津 300072 2. 天津药物研究院 释药技术与药代动力学国家重点实验室，天津 300193 3. 佛罗里达大学 药学院，美国 佛罗里达 32610 摘 要：新药评价已经成为新药研发中最关键的阶段，也是安全合理用药所面临的重大课题。近年来，药动学–药效学 （PK/PD ）模型受到了越来越广泛的关注，这一模型是将PK 和 PD 两个相互关联的动力学过程有机地结合起来，同时探讨机 体对药物的作用及药物对机体的作用，为更全面和准确地了解药物的效应随剂量（或浓度）及时间而变化的规律，从而为临 床用药的安全性和有效性提供更为科学的理论依据。着重综述 PK/PD 模型的发展和在临床前和临床中的应用，证实了 PK/PD 模型可以为新药评价提供有效的理论指导，并大幅度缩短实验周期，节省实验资源，比传统的药物开发策略更加准确可靠。 随着药物评价学的不断完善，模拟软件和模拟条件的标准化，PK/PD 模型在未来的药物开发中必将更充分地发挥其重要作 用并加速药物开发的进程。 关键词：药动学；药效学；PK/PD 模型；药物评价 中图分类号：R969.1 文献标志码：A 文章编号：1674 - 6376 (2011) 03 - 0161 - 06 Application of PK/PD modeling in novel drug evaluation ZHUANG Lu-ning1, 2, 3, GU Yuan1, 2, LIU Chang-xiao2* 1. College of Chemical Engineering, Tianjin University, Tianjin 300072, China 2. State Key Laboratory of Drug Delivery Technology and Pharmacokinetics, Tianjin Institute of Pharmaceutical Research, Tianjin 300193, China 3. College of Pharmacy, University of Florida, Florida 32610, USA Abstract: Drug evaluation has become one of the most critical stages during drug development as well as an important tool to assess the efficacy and safety of novel drugs. Pharmacokinetics/pharmacodynamics (PK/PD) modeling, taking both PK and PD process into consideration and thus comprehensively understanding the relationship between dosing (concentration) and time, has drawn more and more attention from the public recently. By investigating the interaction between the drug and the body system, it provides more valuable information for drug application. In this paper, the development history of PK/PD modeling and its application in preclinical and clinical practice will be discussed. It is now proved