药代动力学比例化剂量反应关系的研究方法及其线性评价  

Evaluation on the methodology of dose proportionality study in clinical pharmacokinetics

作　　者：盛玉成[1] 何迎春[1] 杨娟[1] 郑青山[1] 

机构地区：[1]上海中医药大学药物临床研究中心,上海201203

出　　处：《中国临床药理学杂志》2010年第5期376-381,共6页The Chinese Journal of Clinical Pharmacology

基　　金：国家科技支撑计划基金资助项目(2008BAI51B03);上海市教委基金资助项目(J50303;2008GSP19-5);上海市高校中医内科学E-研究院基金资助项目(E03008)

摘　　要：目的探讨药代动力学比例化剂量反应关系的研究方法及其线性评价。方法利用比例化剂量反应关系可判断药物在体内是否呈线性药代动力学特征,是新药早期临床试验中的基础研究,可为后继的临床试验及剂量调整提供依据。结果基于安全性考虑,早期临床试验的受试者例数较少,给此类研究的设计带来挑战;且几乎所有的药物达到足够高的剂量时,都会呈现非线性特征;评价比例化剂量反应关系不仅检验其是否成立,更重要的是定量评价药代动力学参数和剂量之间的关系。结论目前常用的研究方法有多种,不同方法得出的结论也不尽相同。Objective To evaluate on the methodology of dose propor- tionality study in clinical pharmacokinetics. Methods As a fundamental analysis in early clinical trial, dose proportionality is proposed to assess whether the new agent is linear pharmacokinetics in humans. The results provide useful information in determining the regimen for dosage adjustment in subsequent clinical trials and clinical practice. Results Sample size in early clinical trials was small due to safety purposes,, which creates difficulties for dose proportionality design. Furthermore, since every drug can have nonlinear pharmacokinetics at extreme doses, dose proportionality assessment is not only a hypothesis testing whether it is claimed, but more important a quantitative estimation of relationships between dose and pharmacokinetic parameters. Conclusion Several approaches for the research of dose proportionality are available and they may draw different conclusions even in one study.

关 键 词：比例化剂量反应关系 药代动力学 可信区间 幂函数模型 

分 类 号：R969.1[医药卫生—药理学] R965.2[医药卫生—药学]