Flow cytometric analysis of platelet activation in hypertensive patients. Effect of doxazosin

The percentage of spontaneously activated platelets and the platelet response to several agonists were studied in 26 hypertensive patients. The percentage of platelets expressing glycoprotein (GP) IIb/IIIa in its active conformation (GPIIb/IIIa*), P-selectin and phosphatidylserine (PS) was measured by flow cytometry at baseline and 1 and 2 months after treatment with doxazosin (4 mg/day). The response to ADP and Ca2+ ionophore was also evaluated. The results were compared with those of a control group of 71 normotensive volunteers. Spontaneous platelet activation was higher in patients than in controls (P-selectin-positive results in 4.4+/-2.0% patients vs. 2.7+/-1.7 controls, p<0.05; phosphatidylserine-positive results in 0.7+/-0.4% vs. 0.5+/-0.3%, respectively, p<0.05), and higher in response to ionophore action (phosphatidylserine-positive results 51.8+/-11.1% vs. 43.4+/-11.7%, p<0.01). Platelet activation in patients decreased after 2 months of doxazosin administration compared to baseline (P-selectin-positive results 2.7+/-1.4% vs. 4.4+/-2.0%, p<0.05; phosphatidylserine-positive results 0.3+/-0.2% vs. 0.7+/-0.4%, p<0.05). No significant differences were noted in GPIIb/IIIa*. The clinical significance of normalization of platelet activity by doxazosin remains to be established.     

Lower urinary tract symptoms,pain and quality of life assessment in chronic non-bacterial prostatitis patients treated with α-blocking agent doxazosin; versus placebo

The efficacy of doxazosin monotherapy inchronic non-bacterial prostatitis wasinvestigated in terms of urinary symptom, painand quality of life assessment versus placebo.A total of 60 men with chronic non-bacterialprostatitis were randomised to daily supplementof 4 mg doxazosin or a placebo, for 3 months.International Prostate Symptom Score (IPSS)questionnaire was self administered at theentry and at 3 months after the cessation ofthe treatment. In addition, patients were askedto complete 2-item questionnaire on painrelated symptoms of chronic prostatitis.Quality of life was assessed with a single itemincluded in IPSS.Three months after cessation of the treatmentthere was a significant difference between theoverall mean IPSS, pain and quality of lifescores of the two groups in favour of-blocking agent use (p = 0.001, p <0.001 and p < 0.001, respectively). Inpatients undergone doxazosin treatment;symptom, pain and quality of life statusrevealed 32.94 ± 5.27%, 36.57 ± 5.67%and 36.78 ± 4.75% overall improvement,respectively. IPSS appeared to be a valuabletool in assessing treatment outcome of chronicnon-bacterial prostatitis.     

多沙唑嗪抑制大鼠血管平滑肌细胞增殖的实验研究

为探讨多沙唑嗪对大鼠血管平滑肌细胞增殖的抑制作用。将不同浓度的多沙唑嗪作用于体外培养的血管平滑肌细胞，采用氚-胸腺嘧啶核苷（^3H-TdR)掺入的方法检测平滑肌细胞的增殖。结果发现，多沙唑嗪能够抑制血管平滑肌细胞和不表达α1受体的成纤维细胞的增殖，用不可逆的α1受体阻滞剂酚苄明处理平滑肌细胞，多沙唑嗪仍表现为抑制增殖的作用。以上提示，多沙唑嗪对大鼠平滑肌细胞增殖的抑制作用与其对α1受体的阻滞作用无关。     

多沙唑嗪干预对α_1肾上腺素能受体抗体阳性糖尿病大鼠心肌的保护作用

目的:探讨多沙唑嗪干预对α1肾上腺素能受体自身抗体(α1R-Ab)阳性糖尿病(DM)大鼠心肌转化生长因子β1(TGF-β1)和Ⅰ型胶原表达的影响及其心肌保护作用。方法:Wistar大鼠分为5组:A组(正常对照组,n=10)、B组(DM模型组,n=10)、C组(DM+多沙唑嗪干预组,n=10)、D组(α1R-AbDM组,n=8)和E组(α1R-AbDM+多沙唑嗪干预组,n=8)。腹腔注射链脲佐霉素(STZ)复制T2DM模型。造模成功后,D组和E组于当周、第4、8、12、16周尾静脉注射α1R-Ab注射液(100μg/100g),建立α1R-AbDM模型。C组和E组均从注射α1R-Ab起每日给予多沙唑嗪0.36mg/Kg灌胃,持续16周。A组不予任何处理。16周后处死各组大鼠,取左室心肌组织常规病理切片和超薄切片,采用免疫组化检测左室心肌TGF-β1和Ⅰ型胶原表达量,电镜观察心肌超微结构。结果:A组大鼠心肌TGF-β1和Ⅰ型胶原表达明显低于B、C、D、E组(均P<0.01),C组心肌TGF-β1和Ⅰ型胶原表达低于B组(P<0.05),E组心肌TGF-β1和Ⅰ型胶原表达亦明显低于D组(P<0.05);电镜下,A组心肌未见明显异常;D组心肌线粒体减少,排列紊乱,呈空泡变性,间质胶原增生,微血管基底膜增厚;而E组心肌病变较D组明显减轻;C组心肌病变亦较B组明显减轻。结论:多沙唑嗪可通过抑制α1R-Ab阳性DM大鼠心肌组织中TGF-和Ⅰ型胶原表达,减轻DM大鼠心肌间质纤维化,保护心肌。     

Validated RP-HPLC method for quantification of doxazosin in human plasma: Application in a bioequivalence study

ObjectivesThe aim of the present study was to validate a simple, sensitive, HPLC method of analysis of doxazosin in human plasma with fluorescence detection.MethodsThe validated method employed one-step direct protein precipitation with acetonitrile. Chromatographic separation was attained using a reverse-phase 250 mm × 4.6 mm 5 μ Hypersil® BDS C 18 column and the mobile phase consisted of 10 mm sodium dihydrogen phosphate dihydrate (pH = 3.0) and acetonitrile at a ratio of (65:35 v/v). The method was evaluated in terms of linearity, precision, accuracy, selectivity and stability as per standard guidelines. The total run time was about 4.5 min which make this method suitable for high throughput analyses. This method was applied to the bioequivalence study of two doxazosin tablets in healthy human volunteers.ResultsGood linear response was achieved over the range of 5.0–200 ng/mL. The observed within- and between-day assay precision ranged from 0.64% to 14.73%; accuracy varied between 94.11% and 105%. The 90% confidence intervals for the ratio C max, and AUC 0-∞ of the test product over those of reference were within the acceptable range (0.8–1.25) for bioequivalence.ConclusionThe developed method was simple and could be applied to therapeutic drug monitoring of doxazosin.     

多沙唑嗪与阿替洛尔及特拉唑嗪对照治疗高血压疗效的Meta分析

目的 分析多沙唑嗪与阿替洛尔、特拉唑嗪对照治疗高血压有效性.方法 检索PubMed、EMbase、The Cochrane Central Register of Controlled Trials （CENTRAL）、Medline、中国期刊全文数据库（CNKI）、维普中文科技期刊数据库（VIP）和万方医学数据库等,检索时间从1950年12月至2013年12月.根据纳入与排除标准,收集多沙唑嗪和阿替洛尔、特拉唑嗪对照治疗高血压随机对照试验（RCT）的研究,由2位评价员按Cochrane系统评价,独立进行资料提取、质量评价并交叉核对后,采用RevMan5.2软件进行Meta分析.结果 共10个临床研究符合纳入标准,其中513例患者接受多沙唑嗪治疗,147例患者接受阿替洛尔治疗,353例患者接受特拉唑嗪治疗.Meta分析结果显示,阿替洛尔降低患者坐位舒张压[均数差（MD）=2.35,95％置信区间（CI）：0.47 ～4.23,P=0.00]、坐位收缩压（MD =4.69,95％ CI：2.05 ～ 7.33,P=0.000）、坐位心率（MD=8.96,95％CI：6.21 ～ 11.71,P＜0.00）及站位心率（MD=10.74,95％ CI：8.29 ～13.19,P＜0.01）的作用优于多沙唑嗪.二者对改善患者的站位舒张压（MD=-0.15,95％CI：-2.53～2.22,P=0.90）与站位收缩压（MD =0.61,95％ CI：-2.32 ～3.54,P=0.66）差异无统计学意义.多沙唑嗪与特拉唑嗪对改善患者的坐位收缩压（MD=-0.43,95％ CI：-3.51 ～ 2.65,P=0.79）、坐位舒张压（MD=-0.39,95％CI-1.66 ～0.89,P=0.55）和坐位心率（MD=1.14,95％ CI：-1.02 ～3.30,P=0.30）的作用差异无统计学意义.结论 多沙唑嗪在改善患者坐位血压、心率方面差于阿替洛尔,而与特拉唑嗪相似.对患者站位血压的影响与阿替洛尔相似.     

小剂量睾酮联合多沙唑嗪治疗早泄的临床观察

目的：探讨联合应用口服小剂量十一酸睾酮胶丸（安特尔）和多沙唑嗪控释片（可多华）治疗早泄的效果。方法选择70例早泄病例,按照射精潜伏期的不同,把早泄患者分为3组。均于每晚睡前口服多沙唑嗪4 mg ,每日早、晚餐后口服十一酸睾酮胶丸40 mg。用药3个月后,以射精潜伏期延长＞4 min者为有效,射精潜伏期时间延长3∽4 m in者为改善,射精潜伏期延长但＜3 m in者为无效。结果70例联合应用可多华和十一酸睾酮治疗后,A组有效率为625．％,改善率为25．0％,B组有效率为53．3％,改善率为33．3％,C组有效率为45．3％,改善率为33．3％,总有效率为52．9％,总改善率为31．4％。结论联合应用小剂量睾酮和多沙唑嗪治疗早泄能到达满意的疗效。     

光纤法与进口药品注册标准法测定甲磺酸多沙唑嗪缓释片释放度的比较

摘 要 目的： 比较光纤法与进口药品注册标准法对甲磺酸多沙唑嗪缓释片的释放度测定结果。方法: 采用 FODT-601型光纤药物溶出度实时测定仪,以氯化钠的盐酸水溶液为溶出介质,桨法,转速75 r·min^-1,246 nm作为测定波长,550 nm作为参比波长,测定光程为5.0 mm。比较光纤法与进口药品注册标准法的释放度。结果: 甲磺酸多沙唑嗪在0.468 1～11.700 0 μg·mL^-1浓度范围内线性关系良好,r均大于0.999 5,日内、日间精密度RSD(n=6)分别为1.6%和2.0%,平均加样回收率为99.0%,RSD为1.4%(n=9);比较光纤法与进口药品注册标准法,两者的释放度测定结果有一定差异。结论:光纤法获得的数据信息完整,实时反映,药物的体外溶出过程,在速释和缓、控释制剂的释放度测定中优势尤为突出,但该方法尚不能替代进口药品注册标准法。     

多沙唑嗪治疗留置双J管后的相关症状

目的评价多沙唑嗪对留置双J管患者相关症状的改善作用。方法从2010-01—2012-01间共收集52例输尿管镜下碎石后置入双J管患者,随机分成2组(治疗组、对照组),治疗组26例患者接受了4周多沙唑嗪治疗,剂量为4 mg/d,对照组26例接受安慰剂治疗。所有患者在双J管留置4周时接受USSQ评分。结果治疗组平均排尿症状评分20.9,对照组为26.53,P<0.01,治疗组平均身体疼痛症状评分13.69,对照组为16.77,P=0.021;治疗组平均大体健康指数8.88,低于治疗组的11.08,P=0.017。治疗组平均性问题评分为2.41,低于对照组3.47,P=0.038;带管期间平均生活质量评分治疗组为3.9,低于对照组的4.6,P=0.012。结论多沙唑嗪能够有效治疗留置双J管引起的下尿路症状,缓解疼痛,提高大体健康指数及生活质量。     

甲磺酸多沙唑嗪缓释胶囊的释放度研究

目的建立紫外分光光度法测定甲磺酸多沙唑嗪缓释胶囊的释放度。方法以稀盐酸为释放介质,检测波长245 nm。结果甲磺酸多沙唑嗪在0.419 8～6.716 8μg.mL-1范围内,其浓度与释放度呈良好的线性关系(r=0.999 7),平均回收率为99.54%,RSD为1.89%。结论本方法快速,简便,准确,适用于甲磺酸多沙唑嗪缓释胶囊的释放度测定。