论文部分内容阅读
近年来,群体药物动力学已引起制剂工业以及美国食品药物管理局(U.S Food and Dring Adminis-tration,FDA)专家们的极大关注,不少FDA法规文件中都引用了群体药物动力学来评价药物的有效性和安全性.本文综述了群体药物动力学研究中的群体方法、实验设计、数据处理和分析以及模型的验证等内容,旨在为药品开发和规范管理提供参考.1 研究背景某些疾病的生理病理特征能有规律地改变剂量-浓度之间的关系.例如主要通过肾消除的药物,肾衰通常会引起病人稳态血药浓度的明显升高.群体药物动力学就是研究个体间血药浓度差异的来源和联系,目的在于揭示引起剂量-浓度关系改变的生理病理因素,确定这种改变的大小,以便拟定合适的临床用药剂量.传统药物动力学的研究对象通常是健康志愿者或经严格挑选的病人,且仅对他们的平均情况感兴趣.对于个体间的差异往往采用复杂的实验设计或
In recent years, the group pharmacokinetics have drawn great attention from the formulation industry and the experts of the US Food and Dring Administration (FDA). Many FDA regulatory documents cite population pharmacokinetics to evaluate Drug effectiveness and safety.In this paper, population methods, experimental design, data processing and analysis, as well as model validation in population pharmacokinetics are reviewed in this paper.It is intended to provide a reference for drug development and standardized management.1 Background Physiological and pathological features of these diseases can regularly change the dose-concentration relationship, for example, mainly through the kidney to eliminate drugs, renal failure often leads to a significant increase in patients with steady-state plasma concentration.Pharmacokinetics is the study of individuals The purpose of which is to reveal the physiological and pathological factors responsible for the change in dose-concentration relationship and to determine the magnitude of such change in order to devise a suitable clinical dose.The object of traditional pharmacokinetics is usually healthy volunteer Or by carefully selected patients, and only interested in their average situation.For the differences between individuals often adopt Use complex experimental design or