Efficacy and Safety of Olmesartan Medoxomil and Hydrochlorothiazide Compared with Benazepril and Amlodipine Besylate

BACKGROUND: Most patients with stage 2 hypertension require two or more antihypertensive agents in order to achieve the BP goals recommended in current treatment guidelines. Accordingly, combinations of two drugs with different mechanisms of antihypertensive action are widely used. OBJECTIVE: The aim of this randomized, double-blind, multicenter 12-week study was to compare the efficacy, safety, and tolerability of a combination of olmesartan medoxomil/hydrochlorothiazide (HCTZ) with that of benazepril plus amlodipine besylate in patients with stage 2 hypertension. METHODS: Patients were eligible for randomization following a 3- to 4-week placebo run-in period if they had either (i) mean seated DBP>or=90 mm Hg but<115 mm Hg and mean seated SBP>or=160 mm Hg but <200 mm Hg, or (ii) mean seated DBP>or=100 mm Hg but<115 mm Hg. The difference in mean seated SBP measured on two separate visits during the run-in period was required to beor=95 mm Hg and<115 mm Hg or SBP>145 mm Hg and相似文献   

Central Composite Design for Validation of HPTLC Method for Simultaneous Estimation of Olmesartan Medoxomil,Amlodipine Besylate and Hydrochlorothiazide in Tablets

High performance thin layer chromatographic method for simultaneous estimation of olmesartan medoxomil, amlodipine besylate and hydrochlorothiazide was developed and validated as per ICH guidelines. Moreover, robustness testing was performed applying a central composite design with k factor having 2^k factorial runs, 2k axial experiments and two center points. High performance thin layer chromatographic separation was performed on aluminium plates precoated with silica gel 60F₂₅₄ and toluene:chloroform:methanol:acetonitrile:formic acid (2:7:1.8:0.8:0.2% v/v) as optimized mobile phase. The detection wavelength for simultaneous estimation of three drugs was 232nm. The R_f values for olmesartan medoxomil, amlodipine besylate and hydrochlorthiazide were 0.78, 0.20 and 0.45, respectively. Percent recoveries in terms of accuracy for the marketed formulation was found to be 101.3-104.4, 100.7-104 and 101.5-103.9 for, olmesartan medoxomil, amlodipine besylate and hydrochlorthiazide, respectively. The pooled %relative standard deviation values for repeatability studies and intermediate precision studies was found to be less than 2% for olmesartan medoxomil, amlodipine besylate and hydrochlorthiazide, respectively. All the three factors evaluated in the robustness testing by central composite design were found to have an insignificant effect on the retention factor. However, methanol content in total mobile phase as a factor appeared to have significant effect on robustness, compared to band size and developing distance and hence it is important to be carefully controlled. In summary, a novel, simple, accurate and reproducible high performance thin layer chromatographic method was developed, which would be of use in quality control of these tablets.     

DAD Based Stability Indicating RP-UPLC Method for Simultaneous Determination of Olmesartan Medoxomil and Amlodipine Besylate

Pharmaceutical Chemistry Journal - Stability indicating RP-UPLC-DAD method for simultaneous determination of olmesartan medoxomil (OLM) and amlodipine besylate (AML) in tablet dosage forms has been...     

Spectrophotometric Estimation of Olmesartan Medoxomil and Hydrochlorothiazide in Tablet

A simultaneous determination of olmesartan medoxomil and hydrochlorothiazide by absorption ratio spectrophotometric method has been developed in combined tablet dosage form. The method is based on measurements of absorbance at isoabsoptive point. The Beer''s law obeys in the range of 10–30 μg/ml for both olmesartan medoxomil and hydrochlorothiazide respectively. The proposed method was validated by performing recovery study and statistically.     

Efficacy and Safety Study of Olmesartan Medoxomil,Amlodipine, and Hydrochlorothiazide Combination Therapy in Patients with Hypertension Not Controlled with Olmesartan Medoxomil and Hydrochlorothiazide Combination Therapy: Results of a Randomized,Double-Blind,Multicenter Trial

Background

This study was to evaluate the efficacy and safety of triple fixed-dose combination (FDC) therapy with olmesartan medoxomil (OM) 20  mg, amlodipine (AML) 5 mg, and hydrochlorothiazide (HCTZ) 12.5 mg (OM/AML/HCTZ 20/5/12.5) in Korean patients with moderate hypertension not controlled with dual FDC therapy (OM/HCTZ 20/12.5).

Methods

In this multicenter, randomized, double-blind, parallel-group study, Korean patients aged 20 to 75 years with stage 2 hypertension who had a mean seated diastolic blood pressure (msDBP) ≥100 mmHg were enrolled when their BP was uncontrolled [mean seated systolic BP (msSBP)/msDBP >140/90 mmHg or msSBP/msDBP >130/80 mmHg with diabetes or chronic kidney disease] with 4-week dual FDC therapy (OM/HCTZ 20/12.5). The patients were randomized to receive either OM/AML/HCTZ 20/5/12.5 or OM/HCTZ 20/12.5 once daily for 8 weeks. At the end of 8 weeks, patients with uncontrolled BP were assigned to receive either OM/AML/HCTZ 40/5/12.5 or OM/AML/HCTZ 20/5/12.5 in an additional 8-week open-label extension period.

Results

A total of 623 patients received a 4-week run-in treatment with OM/HCTZ, 341 patients were randomized, and finally, 167 patients in the OM/AML/HCTZ group and 171 patients in the OM/HCTZ group were analyzed for the full analysis set. Non-responders after the 8 weeks of double-blind treatment continued the 8-week open-label treatment with OM/AML/HCTZ 40/5/12.5 mg (n = 32) or OM/AML/HCTZ 20/5/12.5 mg (n = 71). After 8 weeks of double-blind treatment, the changes in msDBP were ?9.50 (8.46) mmHg in the OM/AML/HCTZ group and ?4.23 (7.41) mmHg in the OM/HCTZ group (both p < 0.0001 vs. baseline; p < 0.0001 between groups). The response rates for both msSBP and msDBP at week 8 were 65.27 % in the OM/AML/HCTZ group and 37.43 % in the OM/HCTZ group (p < 0.0001 between groups). The response rates for both msSBP and msDBP at week 16 after open-label treatment were 18.75 % in the OM/AML/HCTZ 40/5/12.5 group and 46.48 % in the OM/AML/HCTZ 20/5/12.5 group (p = 0.0073 between groups). All medications were well tolerated.

Conclusion

In Korean patients with moderate hypertension not controlled with dual FDC therapy (OM/HCTZ 20/12.5) as first-line therapy, switching to triple FDC therapy (OM/AML/HCTZ 20/5/12.5) was associated with significant BP reductions and greater achievement of BP goals, and was well tolerated (ClinicalTrials.gov Identifier: NCT01838850).

     

Efficacy of Olmesartan Medoxomil and Hydrochlorothiazide Fixed-Dose Combination Therapy in Patients Aged 65 Years and Older with Stage 1 and 2 Hypertension or Isolated Systolic Hypertension

Background: The incidence of hypertension, particularly isolated systolic hypertension, increases with in-creasing age, as does the risk of fatal cardiovascular disease. A combination antihypertensive therapy regimen may be required to reach recommended BP goals in older patients. Objectives: This study set out to report blood pressure (BP) data in elderly patients across the subgroups of stage 1 and stage 2 hypertension (prespecified subgroup) and isolated systolic hypertension (ISH) [post hoc]. Design and Setting: This was a subgroup analysis of a prospective, open-label study carried out in a multicenter, outpatient setting (e.g. the BeniSILVER [Benicar Efficacy: New Investigation Shows OM Treatment Increasingly Leads to Various Elderly Populations to Safe BP Reductions; ClinicalTrials.gov identifier: NCT00412932] study). The study included 176 patients with a mean age of approximately 72 years; stage 1 hypertension, 60, stage 2 hypertension, 116, and ISH, 98. Intervention: After a 2- to 3-week placebo run-in period, patients were uptitrated every 3 weeks from olmesartan medoxomil (OM) 20 mg daily to OM 40 mg, OM/hydrochlorothiazide (HCTZ) 40 mg/12.5 mg, and OM/HCTZ 40 mg/25 mg, if seated cuff BP (SeBP) was ≥120/70 mmHg. Measurements: Measurements included change from baseline in mean 24-hour ambulatory BP and SeBP after 12 weeks of treatment, percentage of patients achieving a cumulative SeBP goal of <140/90mmHg (stage 1 and stage 2 cohorts) or seated cuff systolic BP (SeSBP) goal of <140 mmHg (ISH cohort), and the incidence of adverse events (AEs). Results: Combination therapy was required by 159 patients. Changes from baseline in mean 24-hour ambulatory BP (±standard deviation [SD]) were ?24.2 (± 11.8)/?11.8 (± 6.9) mmHg, ?26.5 (± 11.8)/?12.6 (± 6.7) mmHg, and ?24.7 (? 12.5)/?11.2 (± 6.4) mmHg in the stage 1, stage 2, and ISH cohorts, respectively (all p< 0.001 vs baseline). Mean SeBP changes (± SD) from baseline in patients titrated to OM/HCTZ 40 mg/25 mg were ?24.6 (± 11.4)/?10.5 (± 7.3) mmHg in the stage 1 cohort, ?26.4 (± 17.2)/?11.3 (±9.7) mmHg in the stage 2 cohort, and ?21.5 (± 15.6)/?6.8 (± 7.8) mmHg in the ISH cohort (all p <0.001). The cumulative proportions of patients achieving an SeBP goal of <140/90mmHg by week 12 were 88.3%, 56.0%, and 72.4% in the stage 1, stage 2, and ISH cohorts, respectively, while 72.4% of patients achieved an SeSBP of <140 mmHg in the ISH cohort. Treatment-emergent AEs ranged from 32.3% to 32.8%, with <3% of patients reporting drug-related hypotension. Conclusion: An OM/HCTZ-based titration regimen enabled elderly patients with hypertension to safely reduce BP throughout the 24-hour dosing interval and allowed the majority of these patients to achieve a BP target of <140/90 mmHg or <140 mmHg.     

复方苯磺酸氨氯地平/盐酸贝那普利片人体药动学研究

目的研究健康受试者单剂量与多剂量口服复方苯磺酸氨氯地平/盐酸贝那普利片后的药动学。方法LC-MS/MS测定单剂量与多剂量给药后氨氯地平与贝那普利及贝那普利拉血药浓度并利用DAS软件计算药动学参数。结果单剂量给药氨氯地平与贝那普利及贝那普利拉的主要药动学参数分别是:t1/2为(47.3±10.6),(1.3±0.4)和(4.5±0.6)h,Cmax为(6.4±1.5),(136.5±40.2)和(158.3±46.7)μg·L-1,AUC0-t为(267.7±88.4),(144.3±46.7)和(891.4±265.4)μg·h·L-1;多剂量给药氨氯地平与贝那普利的主要药动学参数分别是:t1/2为(45.1±8.7),(1.4±0.4)和(5.3±0.8)h,Cmax为(8.2±1.8),(142.4±47.5)和(165.2±40.8)μg·L-1,AUC0-t为(413.5±102.4),(155.7±52.8)和(915.7±316.9)μg·h·L-1,R为(1.6±0.6)、(1.0±0.1)和(1.2±0.1)。结论复方苯磺酸氨氯地平/盐酸贝那普利片2组分及活性代谢产物在健康受试者体内的吸收速率...     

联合降压治疗老年单纯收缩期高血压的安全性及疗效观察

目的了解贝那普利联合苯磺酸氨氯地平的联合降压治疗对老年单纯收缩期高血压(isolated systolic hypertension,ISH)的安全性及疗效。方法 200例老年ISH患者随机分为治疗组100例,采用贝那普利联合苯磺酸氨氯地平治疗;对照组100例单用贝那普利治疗,4周后对两组的降压有效率,不良反应等指标进行观察。结果 4周治疗组有效率为97.0%(97/100),明显高于对照组,差异有显著性(P<0.05)。两组治疗前收缩压和舒张压比较P>0.05,差异无统计学意义;降压治疗4周后,两组收缩压比较P<0.05,差异有统计学意义;治疗组的降压有效率显著高于对照组,P<0.05,差异有统计学意义;治疗组和对照组出现严重不良反应停药者。结论苯磺酸氨氯地平联合贝那普利治疗老年ISH安全有效,值得各医院推广应用。     

苯磺酸氨氯地平联合贝那普利治疗单纯收缩期高血压临床分析

目的观察苯磺酸氨氯地平联合贝那普利治疗单纯收缩期高血压的疗效。方法随机将150例单纯收缩期高血压患者分为3组,A组50例,口服苯磺酸氨氯地平5.0mg/d;B组50例,口服贝那普利10mg/d;C组50例,口服苯磺酸氨氯地平5mg+贝那普利10mg,1次/d,疗程4周,对比分析3组的疗效。结果 A组、B组与治疗前相比,A组、B组总有效率收缩压下降差异有统计学意义(P<0.05);控制收缩压,苯磺酸氨氯地平联合贝那普利疗效明显大于单纯苯磺酸氨氯地平和贝那普利组(P<0.05)。结论苯磺酸氨氯地平联合贝那普利治疗单纯收缩期高血压的疗效优于单种用药,安全性好。     

HPLC-DAD法检查九味双降素稳安胶囊中非法添加的氢氯噻嗪、苯磺酸氨氯地平

目的：建立HPLC-DAD方法检查九味双降素稳安胶囊中非法添加的氢氯噻嗪、苯磺酸氨氯地平,以打击保健食品中非法添加化学药物现象.方法：采用Phenomenex C18（250 mm×4.6 mm,5μm）色谱柱,以乙腈为流动相A、0.02 mol·L-1磷酸二氢钾溶液（pH3.5）为流动相B进行梯度洗脱,流速为1.0 ml·min-1,柱温为26℃,检测波长为220 nm,进样量为10μl.结果：氢氯噻嗪、苯磺酸氨氯地平线性范围分别为0.24 ～2.43μg（r =0.999 6）;0.08 ～0.80 μg（r =0.999 7）,平均回收率分别为100.2％（RSD=1.4％,n=6）,99.9％（RSD=1.6％,n=6）.结论：本方法选择性强、灵敏度高、处理方法简单、测定快速,可用于九味双降素稳安胶囊中非法添加氢氯噻嗪、苯磺酸氨氯地平的检查.     

奥美沙坦联合苯磺酸氨氯地平治疗原发性高血压的临床观察

目的:观察奥美沙坦联合苯磺酸氨氯地平治疗原发性高血压的疗效及安全性。方法:118例原发性高血压患者随机分为观察组(67例)和对照组(51例)。观察组患者给予奥美沙坦,qd,起始剂量为20 mg/次,视降压情况,剂量可增加至40 mg/次,并给予苯磺酸氨氯地平,qd,5 mg/次;对照组患者仅给予苯磺酸氨氯地平,qd,5 mg/次。两组患者疗程均为6周。观察两组患者临床疗效,治疗前、后的血压(BP)变化及不良反应发生情况。结果:观察组患者总有效率显著高于对照组,两组比较差异有统计学意义(P<0.05);两组患者治疗前舒张压(DBP)、收缩压(SBP)比较差异均无统计学意义(P>0.05),而两组患者治疗后DBP、SBP均显著低于同组治疗前,且观察组显著低于对照组,差异均有统计学意义(P<0.05);所有患者不良反应均可耐受,且未见严重不良反应发生。结论:奥美沙坦联合苯磺酸氨氯地平治疗原发性高血压疗效显著,且安全性尚可。     

延平胶囊中非法添加化学药品的检测方法研究

目的建立TLC结合HPLC法检查保健食品延平胶囊中非法添加的化学药品氢氯噻嗪、苯磺酸氨氯地平。方法采用硅胶GF254板,甲苯-醋酸乙酯-异丙醇-浓氨试液(12:3:3:0.2)为展开剂,在254nm下检视;采用Lichrospher C18柱,流动相:磷酸盐缓冲液(取磷酸二氢钾13.6g,加水80mL溶解后,加磷酸调节pH值至3.0,再加水至100mL)-甲醇-水(4:25:71),流速:1.0mL.min-1,检测波长:225nm,柱温:35℃。结果延平胶囊非法掺入化学药品氢氯噻嗪、苯磺酸氨氯地平在254nm下显明显的斑点。通过HPLC-DAD法进一步验证了结果。结论本法操作简便,结果可靠,可用于检测延平胶囊中非法添加的化学药品氢氯噻嗪、苯磺酸氨氯地平。     

氨氯地平联合替米沙坦或复方阿米洛利的疗效及安全性比较

目的:比较氨氯地平联合替米沙坦和氨氯地平联合复方阿米洛利对轻中度原发性高血压患者的降压疗效和不良反应。方法:选择96例轻、中度原发性高血压患者,按随机及平行对照原则分为氨氯地平/复方阿米洛利组(A组)48例和氨氯地平/替米沙坦组(B组)48例,分别观察两组降压疗效,血生化指标影响及不良反应。观察时间12个月。结果:两组用药后收缩压和舒张压均有显著下降,组间比较差异无统计学意义(P>0.05)。两组治疗前后肝、肾功能及血糖等指标均无变化。A组治疗6月时血钾无变化,12月时血钾升高,6月和12月时尿酸均较入组时明显升高(P<0.05);B组治疗6月和12月时血钾及尿酸较入组时均无明显变化。B组不良反应发生率明显低于A组(P<0.05)。结论:氨氯地平联合替米沙坦与氨氯地平联合复方阿米洛利均有显著的降压效果。氨氯地平联合复方阿米洛利组不良反应发生率明显高于氨氯地平联合替米沙坦组。氨氯地平联合替米沙坦是更优化的联合治疗方案。     

Estimation of Amlodipine Besylate, Valsartan and Hydrochlorothiazide in Bulk Mixture and Tablet by UV Spectrophotometry

A simple, precise, accurate and economic simultaneous UV spectrophotometric method has been developed for the estimation of amlodipine besylate, valsartan and hydrochlorothiazide in combination in bulk mixture and tablet. The estimation was based upon measurement of absorbance at absorbance maxima of 359 nm, 317 nm and 250 nm for amlodipine besylate, hydrochlorothiazide and valsartan in methanol, respectively in bulk mixture and tablet. The Beer Lambert''s law obeyed in the concentration range 5-25 μg/ml, 10-50 μg/ml and 5-25 μg/ml for amlodipine besylate, hydrochlorothiazide and valsartan, respectively. The estimation of bulk mixture and tablet was carried out by simultaneous equation, Q-analysis and area under curve method for estimation of amlodipine besylate and hydrochlorothiazide and standard curve method for estimation of valsartan. The results were found to be in the range of 99.6±1.52% to 102±0.51%. Method was validated with respect to specificity, linearity, range, accuracy, precision, LOD, LOQ, robustness, ruggedness and can be applied for routine analysis of tablet dosage forms.     

奥美沙坦酯治疗轻中度原发性高血压的疗效和安全性

目的评价奥美沙坦酯治疗轻中度原发性高血压的疗效和安全性。方法随机、双盲、双模拟、阳性药物(氯沙坦钾)平行对照。40例轻中度原发性高血压患者随机分为奥美沙坦酯或氯沙坦钾组,均治疗8周,观察两组治疗前后的血压、心率、心电图和血、尿常规等实验室检查结果的变化。结果奥美沙坦酯组与氯沙坦钾组比较,患者平均坐位收缩压和舒张压的降低程度均有显著性差异,分别为(18.9±8.7)mmHg和(12.6±7.6)mmHg(P<0.01);(13.8±3.5)mmHg和(11.7±3.3)mmHg(P<0.05)。治疗前后两组血压降低幅度均有显著差异,心率无明显变化。奥美沙坦酯和氯沙坦钾组降压显效率分别为63.2%和57.9%,总有效率分别为84.2%和68.4%,组间无显著差异。两组共出现3例头晕,实验室检查无异常改变。结论奥美沙坦酯治疗轻中度原发性高血压的疗效良好,不良反应发生率低。     

氨氯地平联合贝那普利治疗难治性高血压的疗效评价

目的 使用氨氯地平联合贝那普利治疗难治性高血压,评价该方案的疗效.方法 前瞻性研究2014年3月至2016年12月期间收治的难治性高血压患者84例.通过随机数字表法分为观察组和对照组,每组各42例.观察组给予氨氯地平片联合贝那普利治疗,对照组单纯给予氨氯地平片治疗,以4周为1个疗程,治疗2个疗程.测量记录两组治疗前及治疗后第4周和第8周时的血压、心率变化情况,并记录治疗过程中有无不良反应,比较两组治疗前后的血压水平以及临床疗效.结果 两组患者治疗前的血压水平相当,差异无统计学意义(P>0.05).治疗后,两组的血压水平均较治疗前低,且观察组的血压水平显著低于对照组,差异有统计学意义(P<0.05).两组患者在治疗前、后心率变化比较差异无统计学意义(P>0.05).观察组的疗效总有效率为88.1%,明显高于对照组总有效率76.2%,差异有统计学意义(P<0.05).结论 氨氯地平联合贝那普利治疗RH起效快,血压控制平稳、效果好,不良反应少,建议临床推广使用.     

Triple-Combination Therapy with Olmesartan, Amlodipine, and Hydrochlorothiazide in Black and Non-Black Study Participants with Hypertension

Background Although awareness of hypertension in Black patients has increased, blood pressure (BP) is frequently inadequately controlled. Objective This prespecified subgroup analysis of the TRINITY study evaluated the efficacy and safety of olmesartan medoxomil (OM) 40 mg, amlodipine besylate (AML) 10 mg, and hydrochlorothiazide (HCTZ) 25 mg triple-combination treatment compared with the component dual-combination treatments in Black and non-Black study participants. Study Design TRINITY was a 12-week, randomized, double-blind, parallel-group evaluation. The first patient was enrolled in May 2008 and the last patient completed the study in February 2009. The study consisted of a 3-week washout period for participants receiving antihypertensive therapy and a 12-week double-blind treatment period. For the treatment phase, all study participants were stratified by age, race, and diabetes mellitus status and randomized to a treatment sequence that led to their final treatment assignment, which they received from weeks 4 to 12 (OM 40 mg/AML 10 mg/HCTZ 25 mg, OM 40 mg/AML 10 mg, OM 40 mg/HCTZ 25 mg, or AML 10 mg/HCTZ 25 mg). In the first 2 weeks of the double-blind treatment period, all participants received either dual-combination treatment or placebo. Participants assigned to dual-combination treatment continued treatment until week 4, and participants receiving placebo were switched at week 2 to receive one of the dual-combination treatments until week 4. At week 4, participants either continued dual-combination treatment or randomly received triple-combination treatment until week 12. Setting 317 clinical sites in the USA and Puerto Rico were included in the study. Patients Study participants eligible for randomization (N = 2492) were ≥18 years of age with mean seated blood pressure (SeBP) ≥140/100 mmHg or ≥160/90 mmHg (off antihypertensive medication). Intervention The intervention was with dual- or triple-combination antihypertensive treatment: OM 40 mg/AML 10 mg/HCTZ 25 mg, OM 40 mg/AML 10 mg, OM 40 mg/HCTZ 25 mg, or AML 10 mg/HCTZ 25 mg. Main Outcome Measure The primary efficacy variable was the change in least squares (LS) mean seated diastolic BP (SeDBP) from baseline to week 12. Secondary efficacy variables included the LS mean change in seated systolic BP (SeSBP), percentage of study participants reaching BP goal, and safety parameters. >Results In both Black and non-Black participants, triple-combination treatment resulted in significant and similar mean reductions in SeDBP and SeSBP (p≤0.0001 vs each dual-combination treatment) with a greater proportion of participants reaching BP goal compared with dual-combination treatments, regardless of race. Most treatment-emergent adverse events were mild or moderate in severity and no new safety concerns were identified. Conclusion Triple-combination treatment provided greater BP reductions than dual-combination treatments regardless of race. Clinical Trial Registration Registered at ClinicalTrials.gov as NCT00649389.