盐酸戊乙奎醚片多次给药人体耐受性试验  

Study on tolerability of healthy volunteers to multiple-dose of penehyclidine hydrochloride medication

作　　者：雍小兰[1] 李楠[1] 杜晓琳[1] 王蓝天[1] 康辉[1] 

机构地区：[1]成都军区总医院临床药学科

出　　处：《中国临床药理学与治疗学》2016年第2期210-213,共4页Chinese Journal of Clinical Pharmacology and Therapeutics

摘　　要：目的:评价健康人体对多次给药盐酸戊乙奎醚片的安全性和耐受性。方法:16名健康受试者经筛选进入临床试验,参与为期7 d的连续给药耐受性试验。根据单次给药耐受性试验结果确定第一组多次给药剂量0.6 mg·次^(-1)·d^(-1),第二组给药剂量0.8 mg·次^(-1)·d^(-1)。观察用药前后受试者临床症状、生命体征,血常规、尿常规、血生化等实验室检查指标变化,并监测心电图,观察和记录不良事件。结果:全部16例受试者均按方案完成试验。部分受试者给药后脉搏和心率出现低于正常范围的情况(P<0.05)。其他生命体征、实验室检查未见有临床意义的改变。两个剂量组全部受试者均有口干、视近物模糊、瞳孔扩大等不良事件,均为本药已知的不良事件且严重程度均为轻度。心电图监测发现有窦性心动过缓和窦性心律不齐的情况,1例受试者部分时间点心电图显示Ⅰ度房室传导阻滞。无严重不良事件发生。结论:盐酸戊乙奎醚片连续7次给药最大耐受剂量为0.8 mg,Ⅱ、Ⅲ期临床试验给药剂量还应结合药代动力学试验结果及临床用药经验确定。AIM： To evaluate the safety and tolerability of penehyclidine hydrochloride in healthy volunteers. METHODS： Sixteen volunteers were randomly administered with a multiple-dose of penehyclidine hydrochloride tablets（ 0. 6 mg,0. 8 mg）for 7 days. The safety profiles and tolerability were evaluated based on vital signs,incidence of adverse events and routine blood and urine test outcomes including blood pressure,heart rate,respiration rate,body temperature,blood biochemistry and electrocardiogram after the administration of penehyclidine hydrochloride tablets. RESULTS： 16 healthy volunteers completed the tolerance tests. In the two groups,the heart rate of post-treatment were significantly decreased than those of pretreatment（ P〈 0. 05）. Xerostomia,blurred vision,mydriasis were observed in the two groups,which were mild adverse events known. Sinus bradycardia and sinus arrhythmia were monitored in healthy subjects. ECG showed first degree atrioventricular heart-block in a subject. Significant changes in other vital signs,laboratory tests,electrocardiogram,serious adverse events were not observed in all subjects in multiple dose trial. CONCLUSION： The multiple medication of penehyclidine hydrochloride at 0. 8 mg one day for 7 days was tolerated. Medication in II and III phase trials shall be combined with test results of pharmacokinetics and clinical experience to determine.

关 键 词：盐酸戊乙奎醚 多次给药 安全性 耐受性 

分 类 号：R969.4[医药卫生—药理学]