卡维地洛片剂Ⅰ期临床耐受性试验报告

Experiment on Tolerance of Carvedilol Tablet in Chinese Healthy Volunteers

目的:研究人体对卡维地洛片剂的耐受程度,找出最大耐受剂量,并根据试验结果为Ⅱ期临床试验提出安全的给药剂量。方法:16位健康志愿者,平均年龄(24.8±6.4)岁(18～45岁)。平均体重(62.5±6.3)Kg(50～72.5Kg)。采用开放试验,随机分为10mg、20mg、30mg和40mg四组,每组4位,男、女各2人。从小剂量组开始,每一受试者只接受一个剂量的试验。试验当天早7时进早餐,8时按分组所规定剂量口服卡维地洛片,用100ml温水送下。分别观察服药前后备时间点的主观症状。卧、立位血压、心率、心律、十二导联心电图及实验室指标。结果:该药对正常人卧、立位收缩压及舒张压有降低趋势.对正常人心率、心律、心电图PR间期、ORS时限、QT间期及QTc、血生化及血、尿常规检查无明显影响。16位健康受试者中,3人(20mg和30mg组)存在头痛及困倦两种症状;1人(30mg组)同时具有头痛、立位收缩压低于90mmHg伴黑朦、便意及耳鸣,持续5分钟;1人(40mg组)服药后立位收缩压低于90mmHg,不能站立,持续4小时。结论:根据以上试验结果,我们认为健康受试者对单次口服40mg(含)以下海南碧凯药业有限公司生产的批号为980408的卡维地洛片耐受性较好,副作用轻微。故高血压国人一次口服卡维地洛片剂量以不大于40mg为宜。

Objective: The purpose of this study is to measure the tolerance of carvedilol tablet and to confirm the available dose range for treatment of hypertension. Methods: Sixteen healthy volunteers (8 males, 8 females) were involved in this open, single - dose trial. They were given 10mg, 20mg, 30mg and 40mg randomly. The supine and standing blood pressure and heart rate were observed, and 12 - lead electrocardiographs and laboratory examination were checked. Results: It was showed that the supine and standing blood pressures decreased significantly in every dose group which the maxim reduction of blood pressure appeared in the period following administrating tablet 2- 6 hour, but heart rate decreased slightly within normal range. Other signs were not changed remarkably within normal range. The pattern of blood pressure didn't change. Three volunteers (20mg and 30 mg) felt headache or dizziness and tiredness. Two volunteers (30mg and 40mg) showed orthostatic hypertension 3h and 4h after administration, respectively . They recovered immediately after lying without any clinic treatment. Conclusion: The result suggests that carvedilol is well tolerated in Chinese healthy volunteers. The therapy of once - daily carvedilol 10-40mg for treating hypertension is available and safe for Chinese hypertensive patients.