HPLC法测定缬沙坦氨氯地平片含量

目的 建立缬沙坦氨氯地平片含量测定的方法.方法 采用Waters Symmetry C18(3.9 mm×150 mm,5 μm),以乙腈∶甲醇∶三乙胺溶液[磷酸调pH(4.3±0.1)]15∶35∶50为流动相,流速1.0 ml·min-1,检测波长237 nm,柱温30℃.以流动相配制对照品及供试品溶液,测定浓度为氨氯地平5 mg·L-1,缬沙坦160 mg·L-1.结果 缬沙坦在128.32~192.48 mg·L-1 范围内线性良好,n=5,r=0.999 7,氨氯地平在4.07~6.14 mg·L-1范围内线性良好,n=5,r=0.999 3.缬沙坦和氨氯地平平均回收率分别为99.93%、99.85%,RSD为0.30%、0.34%.结论 该方法简便快速,灵敏度高,准确可靠.     

单片复方制剂缬沙坦/氨氯地平治疗老年晨峰高血压的临床研究

目的对比观察两种单片复方制剂缬沙坦/氨氯地平（倍博特）与缬沙坦/氢氯噻嗪（复代文）治疗老年晨峰高血压的疗效,为临床提供指导和帮助。方法选择90例治疗或未经治疗的老年原发性高血压患者,全部给予缬沙坦单药80 mg,每天1次,治疗4周后其中58例经动态血压监测具有晨峰血压现象（MBPS）者随机分为两组,观察组换用药物倍博特（n=29）,对照组换用药物复代文（n=29）,每天1次,观察换药治疗4周后24 h平均收缩压（SBP）、24 h平均舒张压（DBP）、24 h平均血压达标率、晨峰血压控制率。结果与换药治疗前比较,2组换药治疗4周后24 h平均SBP和DBP均下降（P〈0.05）,观察组下降幅度大于对照组（P〈0.05）;观察组24 h血压达标率、晨峰血压控制率均高于对照组（P〈0.05）。结论缬沙坦/氨氯地平或缬沙坦/氢氯噻嗪均能有效控制老年原发性高血压患者的血压,但缬沙坦/氨氯地平具有更高的血压达标率及晨峰血压控制率,更适合老年高血压病患者。     

Single-pill combination of amlodipine and valsartan in the management of hypertension

Combination therapy is increasingly recommended for selected patients with hypertension to facilitate prompt attainment and maintenance of goal blood pressure (BP). Single-pill combination therapy simplifies treatment and optimizes long-term compliance. Amlodipine, a dihydropyridine calcium antagonist, and valsartan, an angiotensin receptor blocker, are well-established antihypertensive agents with complementary mechanisms of action. This combination lowers BP significantly more than either of its components, and valsartan reduces the incidence of dose-related amlodipine-induced edema. Rigorous clinical trial data have proven the BP-lowering efficacy and high tolerability of the amlodipine/valsartan combination in patients with moderate to severe hypertension as well as other difficult-to-treat populations. Amlodipine/valsartan is indicated as initial therapy in patients who are unlikely to be controlled with a single drug and as second-line therapy in patients not responding adequately to monotherapy.     

缬沙坦氨氯地平对老年高危高血压患者的疗效及相关影响

目的研究缬沙坦氨氯地平复方制剂对老年高危高血压患者的降压疗效以及对血管内皮功能、氧化应激水平的影响。方法选取在我院就诊的84例老年高危高血压患者,随机分为缬沙坦氨氯地平组(A组,42例,服用缬沙坦氨氯地平复方制剂80/5mg,每日1次)、氨氯地平组(B组,42例,服用氨氯地平单药5mg,每日1次),观察16周,试验结束后比较各组的坐位静息血压水平、血压达标率、血清一氧化氮(NO)、内皮素-1(ET-1)、丙二醛(MDA)含量及超氧化物歧化酶(SOD)的活性。结果治疗结束时,A、B 2组的血压降幅差异有统计学意义(P<0.05),A组的血压达标率与血清NO水平高于B组(P<0.05),ET-1水平低于B组(P<0.05)。A组的血清MDA水平低于B组(P<0.05),SOD活性水平高于B组(P<0.05)。结论对于老年高危高血压患者,应用缬沙坦氨氯地平复方制剂治疗血压达标率更高,能更好地减轻体内的氧化应激水平、保护血管内皮功能。     

缬沙坦/氢氯噻嗪复方制剂和缬沙坦降压疗效的比较

目的:对比缬沙坦/氢氯噻嗪(缬沙坦80mg/氢氯噻嗪12.5mg)复方制剂与缬沙坦(缬沙坦80mg)治疗轻、中度原发性高血压的谷峰比值(TPR)和平滑指数(SI),评价缬沙坦/氢氯噻嗪的降压疗效。方法:选择轻、中度原发性高血压病患者[SBP≥140mmHg且<160mmHg(1mmHg=0.133kPa),DBP≥95mmHg并且<110mmHg]84例,随机分为缬沙坦/氢氯噻嗪和缬沙坦组,共服药8周,观察服药前后血压及生化指标的变化。结果:治疗8周后,缬沙坦/氢氯噻嗪组和缬沙坦组降压有效率分别为84.2、52.5,达标率分别为73.9、42.9,两组间差异有统计学意义(P<0.001)。缬沙坦/氢氯噻嗪组TPR为SBP76.7、DBP71.2,均>50;SI为SBP1.14±0.39、DBP1.09±0.27,均>1。缬沙坦组的TPR为SBP77.6、DBP71.3,均>50;SI为SBP1.24±0.39、DBP1.19±0.27,均>1。两组的TPR和SI差别无统计学意义(P>0.05)。结论:缬沙坦80mg/氢氯噻嗪12.5mg复方制剂治疗轻中度原发性高血压患者疗效优于单用缬沙坦80mg,TPR和SI...     

缬沙坦单药与缬沙坦联合苯磺酸氨氯地平对高血压患者的疗效分析

目的观察缬沙坦联合苯磺酸氨氯地平对高血压患者治疗的临床效果及安全性。方法选取156例高血压患者按入院顺序随机分为2组,对照组76例患者采用缬沙坦80 mg口服,1次/d,观察组80例患者在对照组基础上采用苯磺酸氨氯地平5 mg口服,1次/d,两组患者均治疗6周。对两组患者治疗前后血压、心率、血脂、血糖等进行测定,并根据治疗前后血压下降情况进行疗效评定。同时在治疗期间严密监测两组患者肝肾功能,记录两组患者药物不良反应发生情况。随访两组患者18个月,观察两组患者靶器官损害及心脑血管事件发生情况。结果两组患者治疗前血压比较差异无统计学意义(P>0.05),治疗后两组患者血压均较治疗前明显下降,且观察组治疗后血压均明显低于对照组(P<0.05)。两组患者治疗前后心率比较差异无统计学意义(P>0.05)。观察组治疗总有效率为95.00%,对照组为81.58%,观察组疗效明显优于对照组(P<0.05)。观察组2例(2.50%)出现轻微头痛,对照组1例(1.32%)出现头晕,均无其他严重不良反应发生,两组患者不良反应发生率比较差异无统计学意义(P>0.05)。观察组1例(1.25%)肾功能轻度损害,对照组2例(2.63%)肾功能轻度损害,1例(1.32%)Ⅰ级心功能不全,观察组靶器官损害及心脑血管事件发生率略低于对照组,但两组比较差异无统计学意义(P>0.05)。结论缬沙坦联合苯磺酸氨氯地平治疗高血压,降压效果明显优于单用缬沙坦,并不增加不良反应,而且可降低靶器官损害及心脑血管事件的发生。     

Efficacy and safety of a single-pill combination of amlodipine/valsartan in Asian hypertensive patients inadequately controlled with amlodipine monotherapy

Abstract

Objective:

The antihypertensive efficacy of amlodipine/valsartan combination has not been evaluated in Asian patients as previous large-scale studies enrolled very few patients. This multicentre, randomised, double-blind study assessed the efficacy and safety of a single-pill combination of amlodipine/valsartan versus amlodipine in Asian hypertensive patients.     

缬沙坦氨氯地平片对高血压患者左室舒张功能和动脉顺应性影响的超声学评价

目的应用超声技术评价缬沙坦氨氯地平片（商品名：倍博特）对高血压左心室（LV）舒张功能及动脉顺应性的影响。方法选择90例原发性高血压患者分为LV构型异常组（42例）和LV构型正常组（48例）,均予缬沙坦氨氯地平片1片（含缬沙坦80mg,氨氯地平5mg）,po,qd。分别于给药前、给药3和6个月测量血压、脉压和体质量指数,应用超声心动图测定各受试者左房内径（LAD）、左室内径（LVDd及LVDs）、室壁厚度和相对室壁厚度（RWT）、左室质量指数（LVMI）、左室射血分数（LVEF）;运用多普勒超声和组织多普勒（TDI）分别记录二尖瓣口的血流频谱（E、A、E／A）和二尖瓣环的运动速度频谱（e’、a’）,计算E／e’、e’／a’;运用颈总动脉超声检查测左侧颈总动脉内中膜厚度（IMT）、最大径（Dmax）、最小径（Dmin）,计算颈动脉动脉顺应性（AC）、血管僵硬参数（β）和压力应变弹性系数（Ep）。结果原发性高血压LV构型异常组的e’／a’低于LV构型正常组（P〈0．05）,而E／e’β、Ep高于LV构型正常组（P〈0．05）。给予缬沙坦氨氯地平片治疗3和6个月,与用药前基线值相比,IMT以Ep、E／e’降低（P〈0．05）,AC、e’／a’增高（P〈0．05）,LV构型正常组干预6个月时恢复至正常值范围。LV构型异常组在干预3个月时左室舒张末期容积、每搏输出量恢复至正常值范围,6个月时LAD、RWT、LVMI恢复至正常值范围,但E／e’、e’／a’、β、Ep与LV构型异常组仍有差别（P〈0．05）。结论原发性高血压患者LV舒张功能、动脉弹性的减低,早于动脉结构及心脏构型的改变。缬沙坦氨氯地平片口服3和6个月,对LV构型正常的高血压患者可以改善心脏舒张功能和动脉弹性,对LV构型异常的高血压患者,逆转心脏的重构,形态结构恢复正常,但心脏舒张功能和动脉硬化的参数未完全正常。     

复方缬沙坦/苯磺酸氨氯地平片的制备和体外溶出测定

目的:研制与上市品具有相似体外溶出的复方缬沙坦/苯磺酸氨氯地平片。方法:采用湿法制粒压片工艺制备自制品,通过单因素试验初步筛选处方,中心复合设计优化处方。比较不同pH溶出介质(pH 1.2盐酸、pH 4.5乙酸缓冲液和0.1%聚山梨酯80-pH 6.8磷酸缓冲液)中自制品与市售复方片的溶出行为,通过相似因子f2计算,评价2种药物体外溶出的相似性。结果:与市售片比较,以优化处方制备的复方片中缬沙坦和苯磺酸氨氯地平在不同pH值溶出介质中的溶出度相似因子f 2均>50。结论:自制的复方片与市售片体外溶出行为相似。     

缬沙坦与氨氯地平治疗原发性高血压的比较研究

目的比较缬沙坦和氨氯地平治疗原发性高血压的临床疗效。方法选取2012年12月—2015年12北京市垂杨柳医院老年病科收治的原发性高血压患者121例,随机分为缬沙坦组(n=60)和氨氯地平组(n=61)。缬沙坦组患者口服缬沙坦胶囊,1粒/次,1次/d。氨氯地平组患者口服苯磺酸氨氯地平片,1片/次,1次/d。两组均连续治疗12周。观察两组的临床疗效,同时比较两组治疗前后收缩压、舒张压、心率、总胆固醇(TC)、三酯甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、脂联素(APN)、一氧化氮(NO)、内皮素(ET)的变化情况。结果氨氯地平组和缬沙坦组的总有效率分别为78.69%、80.00%,两组比较差异无统计学意义。治疗后,两组患者收缩压、舒张压、心率、ET均显著降低,APN、NO显著升高,同组治疗前后差异有统计学意义(P0.05)。治疗后,缬沙坦组心率低于氨氯地平组,APN水平高于氨氯地平组,两组比较差异具有统计学意义(P0.05)。结论缬沙坦和氨氯地平治疗原发性高血压均具有较好的临床疗效,缬沙坦可提高患者血浆脂联素水平,改善血管内皮功能,氨氯地平对脂联素水平无显著影响。     

Effects of valsartan versus olmesartan addition to amlodipine/hydrochlorothiazide combination in treating stage 2 hypertensive patients

Objective: The objective of this study was to assess the effects of valsartan or olmesartan addition to dual therapy with amlodipine + hydrochlorothiazide (HCTZ) in the treatment of stage 2 hypertension.

Research design and methods: 180 patients with diastolic blood pressure (DBP) ≥ 99 and < 110 mm Hg were treated with amlodipine 5 mg + HCTZ 12.5 mg combination. After 4 weeks, 149 patients whose blood pressure (BP) was not controlled, were randomized to the combination of valsartan 160 mg + amlodipine 5 mg + HCTZ 12.5 mg or olmesartan 20 mg + amlodipine 5 mg + HCTZ 12.5 mg for 4 weeks.

Main outcome measures: At the end of each period, clinical and ambulatory BP measurements were recorded.

Results: Both triple combinations produced greater ambulatory and clinical SBP/DBP reduction than dual therapy. However, mean reduction from baseline in the valsartan + amlodipine + HCTZ-treated patients was significantly greater than in the olmesartan + amlodipine + HCTZ-treated patients. Compared with dual therapy, the add-on effect of valsartan was significantly greater than that of olmesartan, the difference being more evident for nighttime SBP/DBP values (-3.3 (95% CI 0.44 – 3.51)/3.0 (95% CI 0.59 – 3.34) mm Hg, p < 0.01).

Conclusions: The addition of valsartan to amlodipine + HCTZ produced greater BP reduction than the addition of olmesartan.     

高效液相色谱-串联质谱法测定人血浆中的缬沙坦

目的:建立灵敏、快速的高效液相色谱-串联质谱测定人血浆中缬沙坦浓度的方法,并用于人体药代动力学研究。方法:200μL的血浆样品经乙醚提取处理后,以乙腈-水-甲酸(70∶30∶0.2)为流动相,Diamonsil-C18柱分离,通过电喷雾离子源四极杆串联质谱,以多反应监测(MRM)的方式进行检测,选择监测离子反应为m/z436.3→291.2(缬沙坦)和423.1→207.1(氯沙坦)。结果:缬沙坦在2.120~5 300 ng.mL-1浓度范围内线性关系良好,定量限为2.120 ng.mL-1,日内、日间精密度(RSD)均≤9.0%,准确度在0.9%以内,缬沙坦和内标氯沙坦的回收率分别为83.1%和79.4%。结论:该法选择性强、灵敏度高,适用于缬沙坦的临床药动力学研究。     

缬沙坦或替米沙坦联合氨氯地平在高血压治疗中的效果评价

目的评估缬沙坦或替米沙坦与氨氯地平联合治疗原发性高血压的临床疗效及效价分析。方法选择2014年9-11月我院确诊的原发性高血压患者200例,随机分为2组,缬沙坦组(缬沙坦80 mg,氨氯地平5 mg,1次/d)和替米沙坦组(替米沙坦40 mg,氨氯地平5 mg,1次/d),比较两组的临床疗效、不良反应及效价比。结果治疗8周后,缬沙坦组总有效率为94%,替米沙坦组总有效率为95%,两组总有效率比较差异无统计学意义(P>0.05)。治疗期间,两组患者不良反应发生率差异无统计学意义(P>0.05)。替米沙坦组药物经济学价值高于缬沙坦组。结论缬沙坦或替米沙坦联合氨氯地平在高血压治疗中的降压效果满意,患者耐受性好,不良反应发生率低。替米沙坦联合氨氯地平治疗更能节约用药成本。     

Simultaneous spectrofluorimetric determination of amlodipine besylate and valsartan in their combined tablets

Amlodipine, a dihydropyridine calcium channel blocker, and valsartan, an angiotensin II receptor blocker, are co‐formulated in a single‐dose combination for the treatment of hypertension. The combination is used by patients whose blood pressure is not adequately controlled on either component monotherapy. This work describes a simple, sensitive, and reliable spectrofluorimetric method for the simultaneous determination of the two antihypertensive drugs; amlodipine besylate (AML) and valsartan (VAL) in their combined tablets. The method involved measurement of the native fluorescence at 455 nm (λ_Ex 360 nm) and 378 nm (λ_Ex 245 nm) for AML and VAL, respectively. Analytical performance of the proposed spectrofluorimetric procedure was statistically validated with respect to linearity, ranges, precision, accuracy, selectivity, robustness, detection, and quantification limits. Regression analysis showed good correlation between fluorescence intensity and concentration over the concentration ranges 0.2–3.6 and 0.008–0.080 µg mL^?1 for AML and VAL, respectively. The limits of detection were 0.025 and 0.0012 µg mL^?1 for AML and VAL, respectively. The proposed method was successfully applied for the assay of the two drugs in their combined pharmaceutical tablets with recoveries not less than 98.85%. No interference was observed from common pharmaceutical additives. The results were favourably compared with those obtained by a reference spectrophotometric method. Copyright © 2010 John Wiley & Sons, Ltd.     

Comparative effect of canrenone or hydrochlorothiazide addition to valsartan/amlodipine combination on urinary albumin excretion in well-controlled type 2 diabetic hypertensive patients with microalbuminuria

Objective: To compare the effect of adding canrenone or hydrochlorothiazide (HCTZ) to valsartan/amlodipine combination on urinary albumin excretion (UAE) in microalbuminuric type 2 diabetic hypertensives.

Research design and methods: After a 2-week placebo period and after 4 weeks of valsartan 160 mg plus amlodipine 5 mg combination, 120 patients whose blood pressure (BP) was not controlled (> 130/80 mmHg) were randomized to canrenone 25 mg or HCTZ 12.5 mg in addition to the previous therapy for 24 weeks. After the first 6 weeks of triple therapy, canrenone or HCTZ doses were doubled in the patients whose BP was yet uncontrolled. At the end of each period (placebo, dual combination and triple combination therapy), clinic and ambulatory BP measurements were recorded and 24 h UAE was evaluated.

Results: Both triple combinations produced greater clinical and ambulatory BP reduction than dual therapy, with no difference between the two groups. UAE was reduced by both regimens, but the decrease associated with canrenone add-on therapy was more pronounced. At week 24, UAE decreased by 45.3% in the canrenone group and by 20.3% in the HCTZ group (p < 0.01).

Conclusions: These findings indicate that, despite similar BP-lowering effect, the addition of canrenone to valsartan/amlodipine combination was more effective in reducing UAE than HCTZ addition.     

China STudy of valsartan/amlodipine fixed-dose combination-bAsed long-Term blood pressUre management in HypertenSive patients: a one-year registry (China STATUS III)

Objective: The present observational study evaluated long-term management of hypertension in patients who received treatment with valsartan and amlodipine in a single-pill combination (Val/Aml SPC) in a real-world setting in China (Chinese Clinical Trial Registry number ChiCTR1900021324).

Methods: This was a prospective, observational, multicenter, real-world registry study wherein patients with hypertension who had already received Val/Aml SPC (80/5?mg) for at least 4?weeks before study enrollment were observed for 1?year. Investigators recorded patient data every 3?months and essentially five times during the 1?year follow-up period. Effectiveness was assessed by the blood pressure (BP) control rate and average duration of treatment at the end of the study. Safety was monitored by the incidence of adverse events (AEs) and serious adverse events (SAEs).

Results: Overall, 985 patients were enrolled (mean?±?standard deviation [SD] age: 60.3?±?11.5?years); of these, 894 were included in the full analysis set, 758 of whom completed the study. At baseline, BP was controlled (<140/90?mmHg) in 64.3% of patients on Val/Aml SPC for at least 4?weeks before enrollment. Office BP control rates significantly improved from baseline in 74.1% of patients at 1?year (p?<?.0001). Overall, 575 (87.0%) patients remained on Val/Aml SPC at 1?year (average exposure: 311.5?days). AEs were reported in 23.3% of patients. The majority of AEs were mild to moderate, and 0.6% of patients discontinued Val/Aml SPC because of SAEs.

Conclusion: This study provides evidence that Val/Aml SPC effectively reduced BP over the long term among Chinese hypertensive patients, with a good adherence and tolerability profile, and that most hypertensive patients may benefit from this combination.     

氨氯地平联合缬沙坦治疗肾性高血压的疗效观察

目的分析氨氯地平联合缬沙坦治疗肾性高血压的疗效。方法2011年7月至2012年10月来我院治疗的肾．胜高血压患者40例,随机分为观察组与对照组各20例,观察组患者接受氨氯地平联合缬沙坦治疗,对照组患者接受单纯氨氯地平治疗,治疗1个月后观察两组患者的治疗效果。结果观察组患者的治疗总有效率为80％,对照组患者的治疗总有效率为65％,两组比较差异有统计学意义（P〈0．05）。结论氨氯地平联合缬沙坦治疗肾性高血压临床效果良好,值得临床推广使用。     

氨氯地平联合缬沙坦在轻中度高血压患者中的疗效观察

目的 探讨氨氯地平联合缬沙坦治疗轻中度高血压的效果.方法 根据治疗方法的不同将145例轻中度高血压患者分为A组（55例）、B组（45例）、C组（45例）,A组患者接受氨氯地平联合缬沙坦治疗,B组患者接受氨氯地平治疗,C组患者接受缬沙坦治疗.结果 治疗后,A组患者的SBP、DBP均显著低于B、C组（P＜0.05）,但B组与C组患者的SBP、DBP差异均无统计学意义（P＞0.05）;A组患者治疗显效率明显高于B、C组（P＜0.05）,但B组与C组患者的显效率差异无统计学意义（P＞0.05）.结论 氨氯地平联合缬沙坦治疗轻中度高血压的效果显著优于单一药物治疗,联合治疗方案是治疗轻中度高血压的理想方案.     

缬沙坦联用氨氯地平对老年性高血压左心室构型的影响

目的探讨缬沙坦联合氨氯地平对老年性高血压左心室肥厚及构型的影响。方法将70例高血压患者分成2组,Ⅰ组(n=38)予以缬沙坦联合氨氯地平;Ⅱ组(n=32)单用氨氯地平,2组均给药6 mo后,行24 h动态血压监测(ABPM)和超声心动图检查。结果2组24 h ABPM参数24 h SBP、24 h DBP、dSBP、dDBP、nSBP、nDBP和心脏彩色超声参数IVST、RWT、INMI用药后均较用药前有显著下降,但Ⅰ组优于Ⅱ组(P<0．05)。结论缬沙坦联合氨氯地平在逆转高血压左室肥厚方面有协同作用,且左室构型中向心性重构是防止心肌损害加重的关键阶段。     

沙库巴曲缬沙坦治疗慢性心力衰竭患者的疗效观察

摘要：目的 观察慢性心力衰竭（心衰）患者应用沙库巴曲缬沙坦的临床疗效。方法 连续入选88例慢性心衰 患者,分为ARNI组（47例）和对照组（41例）。ARNI组接受沙库巴曲缬沙坦治疗,对照组接受盐酸贝那普利或缬沙坦 治疗。记录2组患者服药1个月时体质量、24 h尿量、服用利尿剂剂量、N末端B型利钠肽原（NT-proBNP）水平的变化 情况及3个月时心脏结构及心功能的改善情况。结果 ARNI组服药后与服药前比较,患者体质量、服用利尿剂剂 量、NT-proBNP水平均降低,24 h尿量增加,左室舒张末内径（LVDD）及左房内径（LA）均缩小,每搏输出量（SV）、心输 出量（CO）及左室射血分数（LVEF）均升高,二尖瓣环E峰与A峰比值（E/A）较前升高（均P＜0.05）;ARNI组服药后与 对照组比较,患者NT-proBNP水平减低,24 h尿量增多,LVDD及LA均缩小,SV、LVEF和E/A均升高（均P＜0.05）;心 功能分级也较对照组有所改善（P＜0.05）。结论 与盐酸贝那普利/缬沙坦比较,沙库巴曲缬沙坦可进一步减轻钠水 潴留并改善心功能。