Ⅰ类新药布格呋喃的临床耐受性和安全性研究

Tolerance and safety of buagafuran in Chinese healthy volunteers

目的:确定健康受试者对单次和多次口服布格呋喃胶囊的耐受性和安全性。方法:本研究分为单次给药和多次给药两组,单次给药耐受性试验纳入36名健康志愿者,男女各半,分为6个剂量组:15,30,45,60,75和90 mg组,其中包括安慰剂6名。多次给药的耐受性试验纳入10名健康志愿者,男女各半,服用布格呋喃胶囊25 mg,tid,观察9 d。两组的观察指标包括:生命体征、血常规、血生化、电解质、心电图,记录不良事件,7 d后电话随访。结果:所有46名志愿者完成研究。布格呋喃对体温、脉搏和呼吸影响较多,主要是降低脉搏、呼吸次数和体温变化(升高或降低),但是安慰剂组也出现了体温的波动。心电图和实验室检查未见有临床意义的异常。单次给药组36例受试者中安慰剂组6受试者没有不良反应出现,服用药物的受试者有9例出现不良反应,以困倦最多见。连续给药组10例受试者中有8例有不同程度的不良反应,以口干最多见。不良反应均为轻、中度,给予观察或对症处理后均缓解。不良反应的出现与剂量无依赖关系。结论:通过对健康受试者单次和连续给药进行的耐受性试验,结果表明布格呋喃耐受性良好。

Objective： To assess the tolerance and safety of buagafuran in Chinese healthy volunteers taking single or multiple doses.Methods： Healthy volunteers（n=46） were recruited and divided into single and multiple dose groups.Of the volunteers,36 volunteers were randomly divided into six subgroups and volunteers in each group in the turn of dose escalation for the single dose tolerance test.The volunteers in each group received a single dose of buagafuran at 15,30,45,60,75 and 90 mg,respectively,once daily in the morning.There were 2 subjects who took placebo in 45,60 and 75 mg groups,respectively.Other 10 volunteers received multiple doses of 25 mg three times a day for consecutive 7 days.The electrocardiograph,vital signs and laboratory tests were respectively monitored before and after drug administration in the single and multiple dose groups.The adverse effects both observed and spontaneously reported by the subjects were recorded.Results： All the 46 healthy volunteers completed the tolerance test.Significant changes were found in body temperature and heart rate.No significant abnormality in other vital signs,ECG and laboratory tests was found in all of volunteers.The most common adverse effect was mild and dose-independent dry mouth.Conclusion： Buagafuran can be well tolerated in the Chinese healthy volunteers.