Comparative efficacy of two alpha-adrenoreceptor antagonists, doxazosin and alfuzosin, in patients with lower urinary tract symptoms from benign prostatic enlargement

OBJECTIVES: To compare doxazosin and alfuzosin in patients with moderate to severe lower urinary tract symptoms (LUTS) suggestive of bladder outlet obstruction. PATIENTS AND METHODS: In all, 210 men with LUTS were randomized to receive doxazosin 1-8 mg once daily or alfuzosin 5-10 mg divided in two or three daily doses in a 14-week, multicentre, double-blind, baseline-controlled, dose-titration study. The International Prostate Symptom Score (IPSS) and maximum urinary flow rate were used to assess the efficacy of the treatment. RESULTS: At study completion, the mean dose of doxazosin was 6.1 mg/day and alfuzosin 8.8 mg/day. The least squares mean (se) change from baseline in total IPSS was -9.23 (0.6) for doxazosin and -7.45 (0.6) (both P < 0.001) for alfuzosin. The respective mean change from baseline in irritative symptoms was -3.5 (0.2) and -2.8 (0.3) (both P < 0.001). The differences between the treatment groups were statistically significant in favour of doxazosin (total IPSS, P = 0.036; irritative symptoms, P = 0.049). The improvement between groups was also significantly different for postvoid residual urine volume, at -29.19 (8.6) and + 9.59 (8.9) mL for doxazosin and alfuzosin, respectively (P = 0.002). Improvements in mean and maximum urinary flow rates were similar for both treatments, at + 1.5 and + 1.2, and + 2.8 and + 2.5 mL/s, respectively. Doxazosin and alfuzosin were both well tolerated, with most all-cause adverse events reported as mild or moderate. CONCLUSIONS: The mean doses of doxazosin and alfuzosin used in this study were not equipotent. Doxazosin 6.1 mg/day produced significantly greater improvements than alfuzosin 8.8 mg/day in total and irritative urinary symptom scores and postvoid residual urine volume in men with moderate to severe LUTS. Changes in maximum and mean flow rates were comparable. Doxazosin and alfuzosin were both well tolerated.     

Comparison of doxazosin with or without tolterodine in men with symptomatic bladder outlet obstruction and an overactive bladder

OBJECTIVE: To assess the efficacy of combined treatment with doxazosin and tolterodine, as although alpha-blockers are commonly used and generally effective in men with symptomatic bladder outlet obstruction (BOO), a subset of men with BOO and overactive bladder (OAB) symptoms often complain of persistent symptoms. PATIENTS AND METHODS: In a prospective study of 144 consecutive men with BOO at one tertiary urology centre, all had a baseline pressure-flow urodynamic study and were then subdivided into those with BOO or BOO + OAB, based on absence or presence of involuntary detrusor contractions. The Abrams-Griffiths nomogram was used to determine obstructive BOO. After the initial evaluation, all patients were treated with doxazosin 4 mg/day for 3 months. In patients with no symptomatic improvement, tolterodine 2 mg twice daily was added for an additional 3 months. RESULTS: Of the 144 patients, 76 (53%) were diagnosed as having BOO and 68 (47%) BOO + OAB. The patients with BOO + OAB were older (P < 0.05) and had a higher International Prostate Symptom Score. After 3 months of treatment with doxazosin, 60 (79%) with BOO and 24 (35%) BOO + OAB reported a symptomatic improvement. In those patients with no improvement, six of 16 with BOO and 32 of 44 (73%) with BOO + OAB improved after adding tolterodine. Acute urinary retention developed in only two of 60 men (3.3%) treated with the combined therapy. CONCLUSION: About half of men with symptomatic BOO had an OAB; while about three-quarters of men with symptomatic BOO and no OAB improved with doxazosin, only a third with BOO + OAB were helped with doxazosin alone. Combining tolterodine with doxazosin was effective in three-quarters of men with BOO + OAB. Overall, most men with BOO with or with no OAB were helped with doxazosin alone or with the addition of tolterodine.     

HPLC法测定甲磺酸多沙唑嗪含量和有关物质

目的:建立甲磺酸多沙唑嗪及有关物质分离测定的HPLC方法,为原料和制剂的质量控制提供有效的分析手段。方法:色谱柱为Spherisorb C18(250 mm×4.6 mm,5μm);流动相为甲醇-水-冰乙酸-三乙胺(800∶200∶14∶0.6);流速1.0 mL.min-1;检测波长254 nm。结果:甲磺酸多沙唑嗪与各有关物质完全分离,测定了甲磺酸多沙唑嗪及3种有关物质最小检测限。甲磺酸多沙唑嗪在浓度10~120μg.mL-1范围内线性关系良好,相关系数r=0.999 9(n=5);结论:本法操作简便,结果准确,专属性强,灵敏度高,可用于生产质量控制。     

多沙唑嗪控释片和坦索罗辛治疗前列腺增生症的对照研究

目的:评价多沙唑嗪控释片和坦索罗辛治疗良性前列腺增生症(BPH)的疗效。方法:将124例BPH患者随机分为多沙唑嗪控释片组(A组)和坦索罗辛片组(B组),经2周清洗期,2周单盲安慰剂导入期和12周双盲药物治疗期。A组和B组起始剂量分别为4mg/d和0.4mg/d,4周后可分别加量到8mg/d和0.8mg/d。评价指标是国际前列腺症状评分(IPSS)和最大尿流率(Qmax)变化值,以及治疗不良反应发生率。结果:治疗后A组和B组IPSS均降低(P<0.01),且A组优于B组(P<0.001),2组Qmax均增加(P<0.001)。A组无因药物不良反应退出试验,头晕、恶心、体位性低血压等发生率比B组低(P<0.05)。结论:α1受体阻滞剂能有效缓解BPH症状,多沙唑嗪控释片作用全面,有效性和安全性高。     

国产多沙唑嗪片的安全性和降压作用

目的:观察国产多沙唑嗪片在中国健康受试者中的安全性和降压作用,为确定Ⅱ期临床试验的剂量提供依据。方法:采用开放、随机的试验设计,将入选16名健康受试者随机分为4组,每组4名,分别单次口服递增剂量1,2,4,6mg的国产多沙唑嗪片,观察给药后的生命体征、ECC和实验室指标的变化。结果:单次给予多沙唑嗪片1,2,4mg的12名健康受试者,其生命体征、精神状态和行为均无异常变化,虽4mg组有2例出现轻度的头晕、鼻塞等症状,但受试者均能耐受。3名服用6mg受试者,给药后0.5～3.0h出现较严重的头晕、鼻塞、嗜睡、恶心、呕吐、心悸等不良反应,且难以耐受,研究者确认与研究药物有相关性。单次口服不同剂量的多沙唑嗪片后受试者卧、立位SBP和DBP变化:1和2mg剂量组均<10％,幅度均<10mmHg,无体位性低血压发生;4mg剂量组为15％～30％,幅度均<25mmHg,与临床上观察到的体位性低血压发生时间基本一致;6mg剂量组为15％～32％,最大幅度为17mmHg。在1～6mg范围内所有受试者的实验室检查均无异常。结论:考虑到受试者的安全性和耐受程度,临床口服国产多沙唑嗪片的剂量以1～4mg为宜。     

甲磺酸多沙唑嗪胶囊的HPLC测定

建立了测定甲磺酸多沙唑嗪胶囊的HPLC法.色谱柱为Dikma C1 8,流动相为甲醇-醋酸缓冲液(pH3.0)(52:48),紫外检测波长250nm,柱温30℃.在0.5～50μg/ml浓度范围内线性良好,日内日间RSD均小于2%.     

甲磺酸多沙唑嗪治疗高血压的多中心随机双盲临床研究

目的 评价甲磺酸多沙唑嗪片对轻中度原发性高血压的降压疗效及安全性。方法 以盐酸特拉唑嗪为对照,用随机双盲平行多中心临床实验方法,完成病例226例(试验组111例,对照组115例)。起始剂量为每日2 mg,2周末,若舒张压≥90 mmHg,则分别增至每日4 mg,直至增董最高剂量每日6 mg,疗程共8周。另20例开放服用甲磺酸多沙唑嗪的患者,进行动态血压观测,以进行T/P比值分析。结果 两组药物治疗后血压即开始下降。治疗8周末,试验组平均收缩压与舒张压分别下降13.6％和16.1％,对照组分别下降13.7％和16.7％;两组药物的总有效率分别为92.3％和89.2％,两组间临床疗效差异无统计学意义。药物不良反应发生率试验组为17.1％,对照组为15.7％,两组间药物不良反应发生率差异7己统计学意义。结论甲磺酸多沙唑嗪片与盐酸特拉唑嗪片一样,对轻、中度高血压患者的降压疗效确切,药物不良反应轻,病人耐受性好。     

INVESTIGATIONS INTO INTERACTIONS BETWEEN DOXAZOSIN AND ENALAPRILAT AT α1-ADRENOCEPTORS IN ANAESTHETIZED RATS

1. In anaesthetized intact Sprague-Dawley rats, the angiotensin-converting enzyme inhibitor enalaprilat, 1 mg/kg, had no significant effect on the pressor responses to the alpha 1-adrenoceptor agonist phenylephrine (PE). Doxazosin 1 mg kg was found to be a potent alpha 1-adrenoceptor antagonist. 2. The combination of enalaprilat 1 mg/kg plus doxazosin 1 mg/kg was 3.3-fold more potent in antagonizing alpha 1-adrenoceptors than doxazosin 1 mg/kg alone. 3. After treatment of rats with deoxycorticosterone acetate (DOCA) twice weekly for 5 weeks, the alpha 1-adrenoceptor antagonist action of doxazosin in anaesthetized rats was not potentiated by enalaprilat 1 mg/kg. 4. Since DOCA treatment suppresses renin activity, these findings strongly support the hypothesis that angiotensin II can modulate the functional activity of alpha 1-adrenoceptor in vascular smooth muscle.     

INCREASE IN SERUM TOTAL ANGIOTENSIN-CONVERTING ENZYME ACTIVITY WITH ENALAPRIL THERAPY IN HUMANS: A CONTROLLED TRIAL

1. In a controlled, randomized double-blind trial, 15 patients with essential hypertension were treated with enalapril 5-20 mg/day, or doxazosin 1-8 mg/day, during a 7 week dose titration phase. This was followed by 7 weeks of combined treatment with doxazosin and enalapril. 2. Blood was taken after a 2 week placebo run-in phase, and at 3 and 7 weeks in the single-agent and combined treatment phases, for measurement of plasma renin activity (PRA), plasma angiotensin II (AII), plasma aldosterone and serum free and total angiotensin-converting enzyme (ACE) activities. 3. Doxazosin had no effect on serum free or total ACE activities. 4. Enalapril reduced serum free ACE activity and increased serum total ACE activity, which at 7 weeks was significantly greater than in patients receiving doxazosin. 5. In those patients who received enalapril, 10 mg/day for 3 weeks and then 20 mg/day for 4 weeks (n = 12), with or without doxazosin, mean serum total ACE activity increased by 51%. PRA was also increased in this group, but there were no changes in plasma AII or aldosterone concentrations.     

多沙唑嗪对映体不同给药途径对豚鼠膀胱排尿功能的影响

目的比较多沙唑嗪(rac-DOX)及其对映体S-DOX和R-DOX对膀胱排尿功能的影响。方法采用八道生理记录仪连续记录给药前及给药后麻醉豚鼠膀胱排尿压(VMP)、排尿阈值压(MTP)、排尿间隔(ICI)的变化,并测量排尿量(VMV)。结果S-DOX,R-DOX和rac-DOX(0.08~2.40mg.kg-1,经十二指肠插管给药),均可剂量依赖性降低VMP;S-DOX对MTP,ICI及VMV无显著影响;R-DOX则可显著降低MTP;R-DOX和rac-DOX均显著缩短ICI,并减少VMV。S-DOX,R-DOX和rac-DOX(0.008~0.800mg.kg-1,iv),亦可剂量依赖性降低麻醉豚鼠VMP;三者对VMP的作用强度无显著性差异;S-DOX,R-DOX和rac-DOX对MTP无显著影响;S-DOX和R-DOX能显著延长ICI,并增加VMV。结论与R-DOX和rac-DOX相比,S-DOX在保留了原有降低VMP作用的同时,对MTP,ICI及VMV无不良影响。