吲达帕胺对高血压病患者降压作用的临床研究

３４例高血压病患者服国产吲达帕胺后，血压持续缓慢下降，ＴＰＲ显著下降，血浆肾素活性（ＲＡ）、血管紧张素Ⅱ（ＡＴ－Ⅱ）和醛固酮（ＡＤＳ）浓度显著增高，而心率及血儿茶酚爱（ＣＡ）水平无显著变化。治疗４周对全轿Ｃｄ，Ｐｂ，红细胞（ＲＢＣ）及血浆Ｚｎ，Ｃｕ，Ｎａ，Ｋ，Ｍｇ浓度无显著影响。其总疗效为８８．２４％，表明国产吲达帕胺是一种疗效显著而副作用低的降压药物。     

缬沙坦与吲达帕胺联合用药对原发性高血压患者动态血压及胰岛素敏感性的影响

目的：探讨缬沙坦与吲达帕胺联合应用对原发性高血压（EH）患者动态血压及胰岛素敏感性的影响。方法：对65例EH患者于治疗前和治疗24周后分别进行动态血压监测（ABPM）和胰岛素敏感性测定。结果：治疗后24h平均pSB、pDB，血压负荷较治疗前均显著降低（P＜0．01）。治疗后血压昼夜节律消失者8例，较治疗前42例显著减少（P＜0．01）。治疗后各时点胰岛素与血糖比值（I／G）均明显下降（P＜0．01），治疗后胰岛素敏感指数（ISD）显著增高（P＜0．01）；治疗后葡萄糖 耐量试验120min和180min两个时点C／I比值比治疗前显著增高（P＜0．01－0．05）。结论：缬沙坦与吲达帕胺联合应用可显著降低EH患者动态血压水平和血压负荷，改善血压昼夜节律，显著改善胰岛素敏感性。     

氯沙坦单用或与吲达帕胺合用对高血压患者心血管的影响

目的 评价单用氯沙坦或与吲达帕胺合用对高血压患者的心血管结构和功能的影响。方法 40例高血压患者,随机分成氯沙坦单用加量组及氯沙坦与吲达帕胺合用组,疗程均为12周。观察治疗前后随测血压、多普勒彩色心动图指标及动脉脉搏速度（PWV）。结果 两组患者均有显著的血压降低,氯沙坦与吲达帕胺合和组的降压效果较氯沙坦单用加量组更显著（P＜0.05）;两组治疗后左室重量指数（LVMI）、室间隔厚度（LVST）、左室后壁厚度（LVPWT）和动脉脉搏速度（PWV）均有明显下降,E／A比值升高（P＜0.05,P＜0.01）。结论 氯沙坦与吲达帕胺合用有良好的降压作用并能有效改善心血管的结构和功能。     

Pharmacokinetics and bioavailability of indapamide — A new antihypertensive drug

Summary Two formulations of indapamide tablets (2.5 mg) were given as a 5.0 mg dose and the subsequent blood levels were compared to those obtained after administration of a 5.0 mg solution. The study was conducted as a randomized three-way crossover design using healthy male volunteers. The drug was well tolerated by all the subjects involved. The area under the blood concentration versus time curve, extrapolated to infinity was essentially the same for all three formulations (4.2, 4.7, and 4.4 µg-h/ml). Statistical comparison of the blood levels from the two tablets showed that one tablet had a significantly greater maximum blood concentration (263 vs 231 ng/ml) and a significantly shorter time of maximum blood concentration (2.3 vs 3.5 h). C_max (333 ng/ml) and t_max (0.7 h) values for the solution were significantly higher than either tablet. The average half-life (-phase) for all three formulations was 15 h, while the average systemic clearance was 20 ml/min. Indapamide has a low clearance rate and there was no evidence that the drug undergoes a first-pass effect.     

高效液相色谱法测定吲达帕胺的血药浓度

目的建立测定吲达帕胺血药浓度的方法。方法选择以乙腈(pH=2.8)磷酸缓冲液(32∶68)为流动相,格列吡嗪为内标,血浆样品以重蒸乙醚为提取溶剂,经DiamonsilC18(150mm×4.6mm,5μm)柱分离后,在紫外吸收波长240nm处进样40μL检测。结果吲达帕胺血浆样品在25～500ng/mL的范围内线性关系良好(r=0.9996,n=6),绝对回收率>67%,相对回收率>92%日内日间的RSD<6%。结论本法简便、准确、灵敏、重现性好,可用于吲达帕胺的药物动力学的研究。     

替米沙坦与吲哒帕胺联合应用治疗轻、中度高血压的临床疗效

目的 :评价替米沙坦与吲哒帕胺联用治疗轻、中度高血压的临床疗效与安全性。方法 :采用随机平行对照方法 ,将原发性轻、中度高血压患者 73例分成 3组。对照组 (n =2 4 )予替米沙坦 (4 0mg·d-1,qd) ;治疗组Ⅰ (n =2 5 )在服用替米沙坦 (2 0mg·d-1)基础上 ,加服吲哒帕胺 (1 2 5mg ,qd) ;治疗组Ⅱ (n =2 4 )在服用替米沙坦 (2 0mg·d-1)基础上 ,加服酒石酸美洛托尔 (2 5mg ,bid)。疗程均为 8wk。结果 :治疗 8wk后 ,治疗组Ⅰ和治疗组Ⅱ ,总有效率分别为 92 0 %和 83 3% ,前者与对照组总有效率6 2 5 %比较 ,P <0 0 5 ;后者与对照组比较 ,P >0 0 5。对照组、治疗组Ⅰ和治疗组Ⅱ不良反应发生例数分别为 1、3、4例。结论 :低剂量替米沙坦与吲哒帕胺联用治疗轻、中度高血压较单用替米沙坦降压效果好     

Solid-state compatibility screening of excipients suitable for development of indapamide sustained release solid-dosage formulation

Differential scanning calorimetry and Fourier transform infrared spectroscopy were applied as screening analytical methods to assess the solid-state compatibility of indapamide (4-chloro-N-(2-methyl-2,3-dihydroindol-1-yl)-3-sulfamoyl-benzamide) with several polymers aimed for development of 24?h sustained release solid-dosage formulation. After the initial research phase which was directed towards selection of suitable polymer matrices, based on their solid-state compatibility with the studied pharmaceutical active ingredient, the second phase of evaluation was intended for compatibility selection of other excipients required to complete a sustained release formulation. The preformulation studies have shown that polyvinylpyrrolydone/polyvinyl acetate might be considered incompatible with indapamide, and the implementation of this polymer career should be avoided in the case of the entitled development. The experimental data additionally have revealed that sorbitol is incompatible with indapamide. The obtained results afforded deeper insight in to the solid-state stability of the studied binary systems and pointed out directions for further development of indapamide sustained release solid-dosage formulation.     

吲哒帕胺对高血压高危患者血清肌酐、尿酸、血钾及左室肥厚的长期影响

目的　观察吲哒帕胺 (寿比山 )在高血压高危患者中长期应用时SCr、UA、血钾的变化 ,以及合用血管紧张素转换酶抑制剂 (ACEI)能否减轻这些变化。方法　吲哒帕胺组 (Ⅰ组 ) 182例 ,给予吲哒帕胺 2 .5mg/d口服 ,如 2～ 4周后未达到目标血压 (<14 0 / 90mmHg)则加用ACEI苯那普利 (10mg/d)或卡托普利 (2 5～ 75mg/d)。对照组 (C组 )2 10例 ,给予钙拮抗剂 (硝苯地平 30mg/d或非洛地平 5mg/d)或 /和ACEI(苯那普利 10mg/d或卡托普利 2 5～ 75mg/d) ,治疗前后测定SCr、UA、血钾、血脂和血糖并做心超测定左室重量指数。结果　Ⅰ组SCr、UA明显升高 ;Ⅰ组有 7例SCr>2 5 0 μmol/L(而C组为 3例 ,3.8%vs 1.4 % ,P <0 0 5 ) ;7例因UA明显升高而诱发痛风 ;血钾明显降低 (P <0 0 0 1) ,低血钾发生率 14 .8% (C组仅 1.4 % ,P <0 0 0 1)。在Ⅰ组中 ,吲哒帕胺与ACEI合用者与单用吲哒帕胺者相比 ,SCr和UA升高的幅度及血钾降低的幅度明显降低 (P <0 0 1) ,低血钾的发生率亦明显减少 (5 .8%vs 2 5 .3% ,P<0 0 1)。Ⅰ组和C组伴LVH者的LVMI分别减轻 10 8%和 11.5 %。Ⅰ组单用吲哒帕胺的有效降压 (BP <14 0 / 90mmHg)率为 4 9.2 % ,加用ACEI后提高到 85 .3%。结论　吲哒帕胺降压作用肯定 ,长期服用能减轻高血压左室肥厚 ,对     

动态血压监测比较吲哒帕胺和氨氯地平治疗高血压病疗效

目的了解评价吲哒帕胺降压效果并与氨氯地平比较。方法随机选择轻中度的Ⅱ期高血压病１２例，其中６例先予服吲哒帕胺（２．５～５ｍｇ／ｄ），另６例先服氨氯地平（５～１０ｍｇ／ｄ），治疗８周后停药２周，交叉服氨氯地平或吲哒帕胺８周。服每一种药前及８周均行２４小时动态血压监测，并同时监测偶测血压。结果两药治疗后２４小时血压均值、昼间血压均值、夜间血压均值和相应的血压负荷值均显著降低（Ｐ＜０．０１）。两药治疗前后夜间和白昼血压均值比明显下降（Ｐ＜０．０１）。降压效应谷峰比值，两药均＞０．５，但氨氯地平高于吲哒帕胺（Ｐ＜０．０５）。偶测血压监测两药的有效率相似，总有效率均１００％，治疗后血压相显著下降。结论吲哒帕胺和氨氯地平均可持续地控制２４小时血压并具有良好的谷峰比，以及纠正异常的昼夜血压节律作用。但吲哒帕胺价格便宜，故推荐可做为优选的降压药物。