Achari R, Hosmane B, Bonacci E, O'Dea R
Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, Illinois 60064-3537, USA.
J Clin Pharmacol. 2000 Oct;40(10):1166-72.
A double-blind, randomized, placebo-controlled, multicenter study was conducted to describe the dose-response curve for terazosin on blood pressure. A total of 128 patients with mild to moderate essential hypertension (supine diastolic blood pressure, 100 to 114 mmHg) participated in the study. The study consisted of a 4-week single-blind placebo lead-in period and a 14-week double-blind treatment period. Patients were randomized in equal numbers to four parallel treatment groups: terazosin 1, 2, and 5 mg; terazosin 2, 5, and 10 mg; terazosin 20, 40, and 80 mg; and placebo. The 24-hour ambulatory blood pressure measurements were performed at the end of the placebo lead-in period and at the end of each 4-week fixed-dose period. The nonlinear, mixed-effect model computer program was used to analyze the dose-response relationship. There was a strong dose-response relationship between fall in blood pressure and the 1 to 10 mg terazosin dose, as well as a plateauing of response for terazosin doses above 10 mg. The maximum antihypertensive response (Emax) to terazosin was 10.7 mmHg for systolic blood pressure and 8.0 mmHg for diastolic blood pressure. The daily dose of terazosin, which produced 50% of the maximum response (ED50), was 3.0 mg for systolic blood pressure and 1.5 mg for diastolic blood pressure. The results of this study suggest that although some patients may benefit from terazosin doses of greater than 10 mg, doses up to 10 mg will maximize therapeutic benefit for most patients, with acceptable side effects.
进行了一项双盲、随机、安慰剂对照、多中心研究，以描述特拉唑嗪对血压的剂量反应曲线。共有128例轻度至中度原发性高血压患者（仰卧位舒张压为100至114 mmHg）参与了该研究。该研究包括一个为期4周的单盲安慰剂导入期和一个为期14周的双盲治疗期。患者被随机等分为四个平行治疗组：特拉唑嗪1 mg、2 mg和5 mg；特拉唑嗪2 mg、5 mg和10 mg；特拉唑嗪20 mg、40 mg和80 mg；以及安慰剂组。在安慰剂导入期结束时以及每个4周固定剂量期结束时进行24小时动态血压测量。使用非线性混合效应模型计算机程序分析剂量反应关系。血压下降与1至10 mg特拉唑嗪剂量之间存在很强的剂量反应关系，并且特拉唑嗪剂量高于10 mg时反应趋于平稳。特拉唑嗪对收缩压的最大降压反应（Emax）为10.7 mmHg，对舒张压的最大降压反应为8.0 mmHg。产生最大反应50%（ED50）的特拉唑嗪日剂量，收缩压为3.0 mg，舒张压为1.5 mg。本研究结果表明，虽然一些患者可能从大于10 mg的特拉唑嗪剂量中获益，但对于大多数患者，高达10 mg的剂量将使治疗益处最大化，且副作用可接受。
