盐酸戊乙奎醚片单次给药人体耐受性研究

Study on safety and tolerability of single-dose of penehyclidine hydrochloride in healthy volunteers

目的:初步评价健康人体对盐酸戊乙奎醚片单次给药剂量的耐受性,为多次给药及II期临床试验推荐安全剂量。方法:单次给药试验中36例受试者随机分为8个剂量组,分别给予盐酸戊乙奎醚片0.1,0.2,0.3,0.4,0.6,0.8,1.0,1.2 mg。每位受试者只接受1个相应剂量,观察受试者的临床症状、生命体征、实验室检查、心电图检查及不良事件等。结果:实际完成试验方案32例。给药后受试者心率显著减慢(P<0.05),但无剂量依赖性。1.0 mg剂量组视近物模糊的发生率超过50%。心电图检查发现窦性心动过缓和窦性心律不齐情况,个别受试者有I°房室传导阻滞和频发房性早搏等不良事件发生。实验室检查未见有临床意义的异常。结论:盐酸戊乙奎醚片在健康受试者单次给药时安全性和耐受性良好,最大耐受剂量为0.8 mg,推荐多次给药第一组剂量为0.6 mg·d-1。

Objective： To observe the tolerability and safety of penehyclidine hydrochloride in healthy subjects and recommend the safe dosage for multiple dose medication and phase II clinical trial. Methods： Thirty-six healthy volunteers were enrolled in the single dose trial. They received one of the eight dosagees（ 0. 1,0. 2,0. 3,0. 4,0. 6,0. 8,1. 0,1. 2 mg） randomly. The safety was evaluated based on clinical symptoms,vital signs,laboratory tests,electrocardiogram and adverse events. Results： Thirty-two healthy volunteers completed the tolerability test. The post-treatment heart rates were significantly decreased than baseline（ P〈0. 05）,but not dose-dependently. Incidence of blurred vision was more than 50%. Sinus bradycardia and sinus arrhythmia were observed in the subjects. First degree atrioventricular heart-block and frequent atrial premature beats were found in several subjects by electrocardiogram. Significant changes in other vital signs and laboratory tests or serious adverse events were not observed in none of the subjects during the trial. Conclusion： Penehyclidine hydrochloride tablets are well tolerated and safe in healthy volunteers. The maximal tolerance dosage is 0. 8 mg daily. The dose regimen of 0. 6mg·d- 1is recommended for multiple dose medication trials.