Os I, Stokke H P
Department of Nephrology, Ulleval University Hospital, Oslo, Norway.
Blood Press. 1999;8(3):184-91. doi: 10.1080/080370599439724.
Doxazosin, an effective treatment for mild-to-moderate hypertension and benign prostatic hyperplasia, in its standard formulation requires a multiple-step titration regimen to minimize the potential for first-dose effects. A new controlled-release gastrointestinal therapeutic system (GITS) formulation of doxazosin was developed to enhance the pharmacokinetic profile, significantly reducing serum peak-to-trough ratios, thereby minimizing the need for titration. We assessed the efficacy and tolerability of doxazosin GITS compared with doxazosin standard and placebo in a prospective, randomized, double-blind, parallel-group, dose-titration, multicenter study of 392 patients with mild hypertension (blood pressure [BP] < or = 180/95-105 mmHg). Patients were randomized to doxazosin GITS, doxazosin standard, or placebo in 2:2:1 manner. The primary outcome measure was the proportion of patients in the per-protocol analysis (PPA) who achieved goal BP response (sitting BP < or = 90 mmg or 10 mmHg decrease from baseline at 24 h postdose at the final evaluable visit). Goal BP response in the intention-to-treat (ITT) population and prespecified BP and/or heart rate changes in the PPA and/or ITT population were also analyzed. Tolerability was assessed throughout the study. Doxazosin GITS and doxazosin standard produced comparable goal BP responses superior to that of placebo, with 92 of 156 patients (59.0%) on doxazosin GITS and 86 of 152 patients (56.6%) on doxazosin standard in the PPA population achieving goal BP response 24 hours postdose on the final visit, compared with 25 of 70 patients (35.7%) on placebo. Both active treatments produced mean significant BP reductions compared with baseline and placebo (p < 0.001). The most commonly reported side effects were headache, dizziness, and asthenia. No syncope was reported in the doxazosin GITS group; two cases were observed in the doxazosin standard group and one case in the placebo group. Doxazosin GITS was well tolerated and as effective as doxazosin standard in patients with mild hypertension, producing well-tolerated, comparable BP reductions with minimal need for titration. Both active treatments were clinically and statistically superior to placebo.
多沙唑嗪是治疗轻至中度高血压和良性前列腺增生的有效药物，其标准制剂需要多步滴定方案以将首剂效应的可能性降至最低。已开发出一种新的多沙唑嗪控释胃肠治疗系统（GITS）制剂，以改善药代动力学特征，显著降低血清峰谷比，从而减少滴定的必要性。在一项针对392例轻度高血压患者（血压[BP]≤180/95 - 105 mmHg）的前瞻性、随机、双盲、平行组、剂量滴定、多中心研究中，我们评估了多沙唑嗪GITS与多沙唑嗪标准制剂及安慰剂相比的疗效和耐受性。患者以2:2:1的方式随机分为多沙唑嗪GITS组、多沙唑嗪标准制剂组或安慰剂组。主要结局指标是符合方案分析（PPA）中达到目标血压反应（坐位血压≤90 mmHg或在末次可评估访视时给药后24小时血压较基线下降10 mmHg）的患者比例。还分析了意向性治疗（ITT）人群中的目标血压反应以及PPA和/或ITT人群中预先设定的血压和/或心率变化。在整个研究过程中评估耐受性。多沙唑嗪GITS和多沙唑嗪标准制剂产生了可比的目标血压反应，优于安慰剂，在PPA人群中，多沙唑嗪GITS组156例患者中有92例（59.0%）、多沙唑嗪标准制剂组152例患者中有86例（56.6%）在末次访视给药后24小时达到目标血压反应，而安慰剂组70例患者中有25例（35.7%）达到目标血压反应。与基线和安慰剂相比，两种活性治疗均使平均血压显著降低（p < 0.001）。最常报告的副作用是头痛、头晕和乏力。多沙唑嗪GITS组未报告晕厥；多沙唑嗪标准制剂组观察到2例，安慰剂组观察到1例。多沙唑嗪GITS耐受性良好，在轻度高血压患者中与多沙唑嗪标准制剂效果相同，产生耐受性良好、可比的血压降低，且滴定需求最小。两种活性治疗在临床和统计学上均优于安慰剂。
