新药早期临床研究中阳性对照药肝素钠致肝功能损伤的分析和处理  

Analysis and Treatment of Liver Function Injury Caused by Positive Control Drug Heparin Sodium in Early Clinical Studies of New Drugs

作　　者：张薇 杨丹丹[1] 胡殷[1] 王小丹 段一 李琴燕[1] 王志阳 江波[2] ZHANG Wei;YANG Dandan;HU Yin;WANG Xiaodan;DUAN Yi;LI Qinyan;WANG Zhiyang;JIANG Bo(The Second Affiliated Hospital Zhejiang University School of Medicine Nursing Department,Hangzhou 310009,China;The Second Affiliated Hospital Zhejiang University School of Medicine Center of Clinical Pharmacology,Hangzhou 310009,China)

机构地区：[1]浙江大学医学院附属第二医院护理部,杭州310009 [2]浙江大学医学院附属第二医院临床药理中心,杭州310009

出　　处：《中国现代应用药学》2023年第19期2728-2731,共4页Chinese Journal of Modern Applied Pharmacy

基　　金：“重大新药创制”国家科技重大专项(2020ZX09201022)。

摘　　要：目的报道1项新药早期临床研究中阳性对照组输注肝素钠注射液引起肝功能损伤的分析和处理,以期为肝素钠注射液的临床使用提供参考,并为不良反应处理提供思路。方法分析和总结1项以安慰剂和肝素钠注射液为对照,某抗凝新药耐受性和药动学研究中肝素钠组的肝功能损伤不良反应情况,描述病例过程、分析病例情况和处理思路,讨论对早期临床研究分析和处理以及肝素钠临床使用的启示。结果4例健康受试者连续5 d输注肝素钠注射液,3例在给药后出现不同程度谷丙转氨酶和谷草转氨酶升高,考虑为肝素钠注射液所致的药源性肝功能损伤,通过加强指标监测,护肝药物治疗等方式及时进行处理,通过调整方案避免后续其他受试者损伤。结论肝素钠注射液持续输注易引起肝功能损伤,临床使用时应充分关注;早期临床研究应及时分析和处理不良反应,保障受试者安全。OBJECTIVE To report the analysis and treatment of liver function injury caused by heparin sodium injection in the positive control group in an early clinical study of new drugs,in order to provide reference for the clinical use of heparin sodium injection and provide ideas for the treatment of adverse reactions.METHODS Analyzed and summarized one case of liver injury in a tolerance and pharmacokinetics study of a new anticoagulant drug with both placebo and heparin sodium as control,described the case process,analyzed the cause,and discussed the enlightenment for treatment of adverse event in early clinical research and the safety of heparin sodium in clinical use.RESULTS Three cases occurred different degrees increasing of alanine aminotransferase and aspartate aminotransferase after 4 healthy subjects were infused with heparin sodium for 5 consecutive days.It was considered that those were adverse reactions caused by heparin sodium.Timely treatment was performed by strengthening monitoring and administrating liver protective drugs.Protocol was revised to avoid further injury to the follow-up subjects.CONCLUSION Continuous infusion of heparin sodium injection can easily cause liver function damage,and should be given sufficient attention during clinical use.Early clinical research should promptly analyze and handle adverse reactions to ensure the safety of subjects.

关 键 词：肝素钠注射液 早期临床研究 肝功能损伤 连续输注 

分 类 号：R969.4[医药卫生—药理学]