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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: To study the degree of human tolerance to carvedilol tablets and to find out the maximum tolerated dose and to propose a safe dosage for the phase Ⅱ clinical trial based on the results of the test. Methods: Sixteen healthy volunteers, mean age (24.8 ± 6.4) years (18-45 years old). The average body weight (62.5 ± 6.3) Kg (50 ~ 72.5Kg). Using an open trial, were randomly divided into four groups of 10mg, 20mg, 30mg and 40mg, 4 in each group, male and female each 2 people. From the low-dose group, each subject received only one dose of test. The breakfast was served as early as 7 o’clock on the day of the experiment, and at 8 o’clock, the carvedilol tablets were orally administered according to the prescribed dosage and delivered in 100 ml of warm water. Observe the subjective symptoms before and after taking medicine. Lying, standing position blood pressure, heart rate, heart rate, twelve lead ECG and laboratory indicators. Results: The medicine had a tendency to decrease the standing systolic pressure and the diastolic blood pressure in normal people, and there were no significant differences in heart rate, heart rate, ECG PR interval, ORS duration, QT interval, QTc, blood biochemistry and blood and urine Clearly affected. Three of the 16 healthy subjects (20 mg and 30 mg) had headache and drowsiness symptoms. One patient (30 mg) had both headache and systolic blood pressure below 90 mmHg with darkness, tinnitus and tinnitus for 5 Minute; 1 person (40mg group) standing systolic blood pressure after taking less than 90mmHg, can not stand for 4 hours. Conclusion: Based on the above test results, we believe that healthy subjects are less tolerant of carvedilol, batch number 980408, produced by Hainan Bikai Pharmaceutical Co., Ltd. under a single oral dose of 40mg (inclusive) with minor side effects. Therefore, an oral high-blood pressure carvedilol tablets to not more than 40mg appropriate.