泰克吉宁注射液静脉给药临床耐受性试验-第三军医大学学报.docVIP

泰克吉宁注射液静脉给药人体耐受性研究 侯鑫，徐楠▼，刘春涛，郑莉，王颖 (四川大学华西医院药物临床研究机构,成都 610041) 摘要: 目的 评价健康志愿者对泰克吉宁注射液的耐受性38名健受试者单次给药、续给药泰克吉宁注射液泰克吉宁注射液(Institution of Drug Clinical Study of West China Hospital, Sichuan University, Chengdu 610041, China) Abstract: Objective To evaluate the tolerance of Taikejining in healthy volunteers after intravenous infusion administration, to determine the dose of single and continuous use and to provide the evidence of phase Ⅱ clinical trial. Methods Thirty-eight healthy subjects joined in single administrating trial, receiving Taikejining at 50, 100, 200, 350, 500, 650 and 750 mg. Six healthy subjects in continuous administrating study, were given 400 mg bid for five days. We observed subjects’signs, clinical syndromes and laboratory test results. Results No severe adverse events happened in the trial. One subject who was dizzy on the fifth day in the continuous administrating trial, recovered after taking the oral pills when the test was over, indicating that the dizziness may be not related to the drug. Conclusion It is safe and tolerated to take Taikejining under 750 mg in single intravenous infusion administration and 400 mg bid administrating in continuous infusion for five days. Therefore, 400 mg bid is suggested to be the administrating protocol in phase Ⅱ clinical test. Key words: Taikejining; Clinical Tolerance Trial 泰克吉宁注射液中药射干提取物鸠尾苷元磺酸钠的灭菌水溶液，具有抗病毒、抗炎、解热、镇痛的作用，用于治疗急性呼吸道感染及病毒性肺炎。根据国家食品药品监督管理局药物临床研究批件（批件号2006L00092）I期病房进行了泰克吉宁注射液I泰克吉宁注射液0mg/2ml，由四川迪康科技药业股份有限公司提供250ml生理盐水稀释后静脉滴入60min滴完。心脑血管、肺、肝、肾造血系统有药物、食物等过敏者妊娠期、哺乳期、月经期妇女每受试者只接受一个相应的剂量，从小剂量开始，每个剂量结束观察至少3天，对该组剂量进行安全性评价，未达到中止试验标准，则继续进行下一个剂量组试验。如出现较重不良反应或如半数受试者出现轻度不良反应，即使未达到最大剂量，均应停止试验。采用改良Blac well 法，根据急毒实验LD50的1/600及动物长期毒性实验中出现毒性剂量的1/60，选择以上剂量的最小值作为最小初始剂量用动物在长期毒性实验中引起功能或脏器可逆性损害剂量的1/10，或动物长期毒性实验中最大耐受量的1/5～1/2的作为估计的最大耐受量泰克吉宁注射液小鼠急性毒性实验LD50? kg-1，? d-1；长期毒性试验结果表明，? kg-1? d-1出现脏器系数增加，Beagle犬连续28天mg? kg-1? d-1剂量组起可出现。结合临床可操作性泰克吉宁注射液规格为mg/安按体重60kg/人确定泰克吉宁注射液单次给药成人初始剂量为mg/d（相当于1安）最大耐受量为g/d。参照费氏递增法