Chalmers J, Tiller D, Horvath J, Bune A
Lancet. 1976 Aug 14;2(7981):328-31. doi: 10.1016/s0140-6736(76)92589-7.
The effects of timolol (10 mg thrice daily) and hydrochlorothiazide (50 mg/day) have been compared in a double-blind factorial trial in 20 patients with essential hypertension. There were four randomised test phases of 8 weeks each during which patients received timolol alone, hydrochlorothiazide alone, timolol plus hydrochlorothiazide, and no treatment (placebo). Blood-pressure was measured weekly, alternately at the outpatient clinic and at the patient's home. Supine mean arterial pressure fell from 119 mm Hg in the placebo phase to 110 mm Hg in the hydrochlorothiazide phase, 106 mm Hg in the timolol phase, and 101 mm Hg in the combined timolol plus hydrochlorothiazide phase. Factorial analysis revealed that these effects of the two drugs were additive without any potentiation or antagonism. Mean plasma-renin activity (P.R.A.) was 5-02 ng/ml/3 h in the placebo phase falling to 1-79 in the timolol phase and rising to 9-54 in the diuretic phase, but remaining unchanged in the combined treatment phase (5-40 ng/ml/3 h). The data suggest that the hypotensive action of timolol is not dependent on the concomitant fall in P.R.A. The methods described provide a valuable tool for quantitating the effects of a given drug, and hence a valid basis for objective comparison.
在一项双盲析因试验中，对20例原发性高血压患者比较了噻吗洛尔（每日3次，每次10毫克）和氢氯噻嗪（每日50毫克）的疗效。试验分为四个随机测试阶段，每个阶段为期8周，在此期间患者分别接受单独使用噻吗洛尔、单独使用氢氯噻嗪、噻吗洛尔加氢氯噻嗪以及不治疗（安慰剂）。每周测量血压，交替在门诊诊所和患者家中进行。仰卧位平均动脉压从安慰剂阶段的119毫米汞柱降至氢氯噻嗪阶段的110毫米汞柱、噻吗洛尔阶段的106毫米汞柱以及噻吗洛尔加氢氯噻嗪联合阶段的101毫米汞柱。析因分析显示，这两种药物的作用是相加的，没有任何增强或拮抗作用。平均血浆肾素活性（P.R.A.）在安慰剂阶段为5.02纳克/毫升/3小时，在噻吗洛尔阶段降至1.79，在利尿剂阶段升至9.54，但在联合治疗阶段保持不变（5.40纳克/毫升/3小时）。数据表明，噻吗洛尔的降压作用不依赖于同时出现的血浆肾素活性下降。所描述的方法为定量给定药物的效果提供了有价值的工具，因此是进行客观比较的有效基础。
