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。
Starting dose of first- in- human clinical trial （FIH） is most crucial for the success of clinical trial. Full consideration of pharmacody- namics, toxicity and pharmacokinetics should be taken as estimating the FIH starting dose to protect the safety of subjects by avoiding adverse reaction induced by exaggerated dosing, and get the expected endpoint fast without increasing unnecessary sample size. In this paper, methods of pharmacokinetics in human at intended effect levels extrapolated by the corresponding exposures of pharmacological or toxicological levels from preclinical studies are introduced in detaiL, and then the topics of FIH starting dose determined by comparing different results are also illustrated to decrease the risk efficiently and elevate the success rate of FIH clinical trial.
出处
《中国临床药理学杂志》
CAS
CSCD
北大核心
2016年第24期2341-2344,共4页
The Chinese Journal of Clinical Pharmacology
