药代动力学在创新药物首次人体试验起始剂量计算中的意义

发布时间：2019-07-21 16:44

【摘要】：首次人体试验起始剂量选择是否合理直接关系到试验的成败,在确定起始剂量时,需要综合考虑已有的动物药效、毒性及药代动力学研究数据,既要避免因起始剂量过大导致严重不良反应以保证受试者安全,又要考虑在不过多增加受试者数量的情况下较快达到试验目标。本文详细介绍了根据临床前体外或体内毒性和药理活性水平的暴露量,推算相应的人体药动力学参数,综合考虑药物作用及靶点特征,获得预期人体药效学或毒性剂量,比较并确定合理的首次临床试验起始剂量的方法,以期有效降低首次人体试验风险,提高试验成功率。
[Abstract]:Whether the initial dose selection of the first human trial is reasonable or not is directly related to the success or failure of the test. In determining the initial dose, it is necessary to comprehensively consider the existing animal efficacy, toxicity and pharmacokinetics data, not only to avoid serious adverse reactions caused by the excessive initial dose to ensure the safety of the subjects, but also to consider achieving the test goal quickly without increasing the number of subjects. In this paper, according to the exposure of toxicity and pharmacological activity in vitro or in vivo before clinic, the corresponding pharmacokinetics parameters were calculated, the expected pharmacokinetics or toxic dose was obtained by considering the characteristics of drug action and target, and the reasonable initial dose of first clinical trial was compared and determined in order to effectively reduce the risk of the first human trial and improve the success rate of the trial.
【作者单位】：国家食品药品监督管理总局药品审评中心;
【分类号】：R969.1

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