Rotmensch H H, Vlasses P H, Swanson B N, Irvin J D, Harris K E, Merrill D G, Ferguson R K
Am J Cardiol. 1984 Jan 1;53(1):116-9. doi: 10.1016/0002-9149(84)90694-5.
The effects of the new nonsulfhydryl-containing oral converting-enzyme inhibitor MK-521 on blood pressure, heart rate, angiotensin-converting enzyme activity, plasma renin activity and plasma aldosterone concentration were assessed in 10 hypertensive patients. After a 2-week no-treatment period, patients received placebo and then 14 days each: MK-521 20 mg once daily, hydrochlorothiazide 50 mg once daily and the latter 2 in combination. During the last day of each treatment, the mean (+/- standard deviation) time-averaged (1- to 12-hour) standing diastolic blood pressure decreased from 106 +/- 8 (placebo) to 95 +/- 10 mm Hg with MK-521, 95 +/- 13 mm Hg with hydrochlorothiazide (p less than 0.05 vs placebo) and 88 +/- 11 mm Hg with the combination (p less than 0.05 vs all other treatments). The antihypertensive effect of MK-521 was maintained 24 hours after dosing. Heart rate did not change significantly after MK-521 treatment. MK-521 caused a marked suppression of converting enzyme activity for over 24 hours; plasma renin activity increased significantly after each active treatment and MK-521 significantly decreased the hydrochlorothiazide-induced elevation of plasma aldosterone concentration. In this short-term trial, MK-521 was well tolerated.
在10例高血压患者中评估了新型不含巯基的口服转化酶抑制剂MK - 521对血压、心率、血管紧张素转化酶活性、血浆肾素活性和血浆醛固酮浓度的影响。在为期2周的未治疗期后，患者先接受安慰剂治疗，然后分别接受以下治疗各14天：MK - 521每日1次，每次20 mg；氢氯噻嗪每日1次，每次50 mg；以及二者联合使用。在每种治疗的最后一天，平均（±标准差）1至12小时站立位舒张压，使用MK - 521时从安慰剂组的106±8 mmHg降至95±10 mmHg，使用氢氯噻嗪时降至95±13 mmHg（与安慰剂相比p<0.05），联合使用时降至88±11 mmHg（与所有其他治疗相比p<0.05）。MK - 521给药后24小时仍保持降压效果。MK - 521治疗后心率无显著变化。MK - 521可使转化酶活性显著抑制超过24小时；每种活性治疗后血浆肾素活性均显著升高，且MK - 521可显著降低氢氯噻嗪引起的血浆醛固酮浓度升高。在这项短期试验中，MK - 521耐受性良好。
