国产多沙唑嗪片的安全性和降压作用

Safety and efficacy of domestic doxazosin tablet in healthy Chinese volunteers

目的:观察国产多沙唑嗪片在中国健康受试者中的安全性和降压作用,为确定Ⅱ期临床试验的剂量提供依据。方法:采用开放、随机的试验设计,将入选16名健康受试者随机分为4组,每组4名,分别单次口服递增剂量1,2,4,6mg的国产多沙唑嗪片,观察给药后的生命体征、ECC和实验室指标的变化。结果:单次给予多沙唑嗪片1,2,4mg的12名健康受试者,其生命体征、精神状态和行为均无异常变化,虽4mg组有2例出现轻度的头晕、鼻塞等症状,但受试者均能耐受。3名服用6mg受试者,给药后0.5～3.0h出现较严重的头晕、鼻塞、嗜睡、恶心、呕吐、心悸等不良反应,且难以耐受,研究者确认与研究药物有相关性。单次口服不同剂量的多沙唑嗪片后受试者卧、立位SBP和DBP变化:1和2mg剂量组均<10％,幅度均<10mmHg,无体位性低血压发生;4mg剂量组为15％～30％,幅度均<25mmHg,与临床上观察到的体位性低血压发生时间基本一致;6mg剂量组为15％～32％,最大幅度为17mmHg。在1～6mg范围内所有受试者的实验室检查均无异常。结论:考虑到受试者的安全性和耐受程度,临床口服国产多沙唑嗪片的剂量以1～4mg为宜。

AIM: To study the safety and influence of domestic doxazosin on blood pressure properties after oral ad ministration in Chinese healthy volunteers. METHODS: The study was opened and randomized. Four groups, each of 4 subjects, were given single ascending doses ranging from 1 mg to 6 mg. The changes of blood pressure, vital signs and laboratory values were recorded. RESULTS: It was shown that 1, 2 and 4 mg dosage group did not influence the vital signs significantly, and there were no changes in the mental or behavioral status. When 6 mg single dose was taken, all 4 volunteers displayed nausea, vomiting, dizziness, staffy nose, sleepy and palpitation inspectively. There were no any changes to be found in laboratory values of haematology, biochemistry and urinalysis during the dose of 1 - 6 mg. CONCLUSION : The result suggest that the safe dose of doxazosin may range from 1 mg to 4 mg. It is well tolerated from all perspective studies during this dose and shows a potent anti-high blood pressure property.