新药早期临床试验中的定量药理学方法

Pharmacometrics in early clinical trials of new drugs

定量药理学是一个工具学科,即建模、模拟和预测。本文通过几个常用的定量药理学模型在新药早期临床试验的应用范例,说明其独特的重要价值,包括药代动力学/药效动力学(PK/PD)模型、特殊人群的生理药代动力学(PBPK)模型、基于机制的PK/PD模型、暴露-反应(E-R)模型、基于模型的meta分析(MBMA)。此类模型可以整合众多的试验结果和文献数据,可提取到常规方法无法获得的信息,能够进行模拟预测,为后续临床试验设计提供依据,从而加快研究进度,减低风险。

Pharmacometrics is a useful tool, including modeling, simulation and prediction. Through studies of pharmacokinetics/pharmacodynamics （PK/PD） , physiological pharmacokinetics （PBPK） in special populations study, mechanism-based pharmacokinetic/pharmacodynamic, exposure-response relationship （E-R） and model-based meta-analysis （MBMA） , the specific applications of these commonly used pharmacometrics analyses were demonstrated in early clinical trials of drugs, and the value of pharmacometrics was shown. Information that is indiscernible to the traditional methods is extracted from a large amount of studies and literature with some quantitative models. Pharmacometrics makes the drug development decision effective, shortens the developing cycles and reduces the level of risk.