药物动力学和药效动力学在抗菌药物新药开发和临床治疗上的应用

摘要/Abstract

摘要： 制定合理的给药方案是抗菌药物开发中临床试验成败的关键。近十年来群体药物动力学和药效动力学的发展和在抗菌药新药开发上的应用, 对抗菌药物合理给药方案的制定有了突破性进展, 已基本上形成了抗菌药物新药开发的一个模式。这一模式以药动药效学理论指导下的体外动力学模型、动物体内感染模型和I 期临床药动学试验为基础, 以随机化统计模型和蒙地卡罗模拟为手段对III 期临床试验的给药方案进行统计比较以确定最佳的给药剂量和频率。本文系统性地描述如何从临床前和临床试验中获得准确可靠的数据进而建立药动药效学数学模型, 着重于阐述抗菌药物药效学的基本概念、试验方法学的基本原理并简单介绍药动药效学的计算方法。

关键词: 药动学, 药效学, 抗菌药物, 体外动力学模型, 蒙地卡罗模拟

Abstract: Integration of pharmacokinetics (PK)/pharmacodynamics (PD)in antibiotic drug development allows the dosage regimen to be optimized, so that the desired effect can be achieved in a large proportion of the target patient population.In vitro kinetic and in vivo animal models have been extensively used in the evaluation of antibiotics.The value of these pre-clinical models in the PK and PD characterization of antibiotics is critically reviewed.A model based clinical development of antibiotics with integrating MIC distribution, PK parameter distribution, the PD target from animal models of infection, and the protein binding of the test drug, is also reviewed.

Key words: pharmacokinetics, pharmacodynamics, antibiotic, in vitro kinetic model, Monte Carlo simulation

中图分类号:

R969

史军. 药物动力学和药效动力学在抗菌药物新药开发和临床治疗上的应用[J]. 中国临床药理学与治疗学, 2007, 12(2): 121-133.

SHI Jun. Integration of pharmacokinetics and pharmacodynamics in antibiotic drug development and pharmacotherapy[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2007, 12(2): 121-133.

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