Alderman E L, Davies R O, Crowley J J, Lopes M G, Brooker J Z, Friedman J P, Graham A F, Matlof H J, Harrison D C
Circulation. 1975 Jun;51(6):964-75. doi: 10.1161/01.cir.51.6.964.
Seventeen patients received placebo medication during a 12-week run-in period, followed by four double-blind study periods of six weeks each, during which time placebo, 80 mg, 160 mg and 320 mg propranolol dosages were administered. Examination of the frequency of angina episodes and nonprophylactic nitroglycerin consumption revealed significant beneficial clinical responses for both the 160 and 320 mg dosages. Exercise testing also demonstrated increased exercise tolerance (320 mg dose) with a shift of the exercise end point from pain to fatigue in seven of 17 patients. The interrelationships between propranolol daily dosage, clinical response assessed by percent reduction in anginal episodes, beta-adrenergic blockade measured by percent reduction in exercise heart rate and serum levels were examined. In general, serum levels of 30 ng/ml, when drawn 90 to 180 minutes following the last oral dose, were required to achieve a 25% or greater reduction in angina frequency. Serum levels above 30 ng/ml were similarly correlated with a 20% or greater reduction in exercise heart rate at equivalent levels of exercise. Detailed examination of different patterns of clinical response with respect to beta-blockade, serum levels and oral doses are presented.
17名患者在12周的导入期接受安慰剂治疗,随后进入四个为期六周的双盲研究阶段,在此期间分别给予安慰剂、80毫克、160毫克和320毫克的普萘洛尔剂量。对心绞痛发作频率和非预防性硝酸甘油消耗量的检查显示,160毫克和320毫克剂量均产生了显著的临床有益反应。运动试验还表明运动耐力有所提高(320毫克剂量),17名患者中有7名患者的运动终点从疼痛转变为疲劳。研究了普萘洛尔每日剂量、通过心绞痛发作减少百分比评估的临床反应、通过运动心率降低百分比测量的β-肾上腺素能阻滞与血清水平之间的相互关系。一般来说,在最后一次口服给药后90至180分钟采血时,血清水平达到30纳克/毫升才能使心绞痛频率降低25%或更多。在同等运动水平下,血清水平高于30纳克/毫升同样与运动心率降低20%或更多相关。本文详细介绍了关于β-阻滞、血清水平和口服剂量的不同临床反应模式。