Olmesartan medoxomil: in children and adolescents with hypertension

Olmesartan medoxomil is an orally administered angiotensin II receptor antagonist, selective for the angiotensin II type 1 receptor, which has established antihypertensive efficacy in adults. In children and adolescents with hypertension (n?=?302), oral olmesartan medoxomil significantly and dose-dependently reduced seated systolic blood pressure (BP) and seated dystolic BP from baseline (the primary endpoint) in a 3-week, dose-response period in a well designed phase II/III clinical trial. Patients received olmesartan medoxomil high dose (20 or 40?mg once daily depending on bodyweight) or low dose (2.5 or 5.0?mg once daily depending on bodyweight). The response was significant for both cohorts, which were stratified by race (cohort A was mixed race [62% White] and cohort B was 100% Black). In addition, BP control was maintained in olmesartan recipients relative to placebo recipients in cohort A and the combined cohort A?+?B, but not for patients in cohort B, during a placebo-controlled withdrawal period of this trial. Oral olmesartan medoxomil was generally well tolerated in children and adolescents with hypertension. The majority of adverse events were of mild to moderate intensity.     

Olmesartan medoxomil/amlodipine/hydrochlorothiazide: fixed-dose combination in hypertension

The antihypertensive agents olmesartan medoxomil, amlodipine and hydrochlorothiazide (HCTZ) are now available as a fixed-dose combination tablet (olmesartan medoxomil/amlodipine/HCTZ). In a 12-week, randomized, double-blind, multicentre trial (TRINITY) in adults with moderate to severe hypertension, olmesartan medoxomil?+?amlodipine?+?HCTZ triple combination therapy produced significantly greater least squares mean reductions from baseline in seated diastolic blood pressure (BP) [primary endpoint] and seated systolic BP than olmesartan medoxomil/amlodipine, olmesartan medoxomil/HCTZ or amlodipine?+?HCTZ. Furthermore, significantly more patients achieved BP goals and targets with the triple combination regimen than with any of the dual combination regimens at week 12, with olmesartan medoxomil?+?amlodipine?+?HCTZ also demonstrating benefit over the dual regimens in terms of ambulatory BP control. According to subgroup analyses of the TRINITY trial, olmesartan medoxomil?+?amlodipine?+?HCTZ was more effective in reducing BP and achieving BP goals than each of the dual therapies, irrespective of hypertension severity, age, sex, race or diabetes mellitus status. Data from a number of smaller clinical studies indicated that olmesartan medoxomil?+?amlodipine?+?HCTZ triple combination therapy provides antihypertensive efficacy in patients whose BP is not adequately controlled with olmesartan medoxomil?+?amlodipine. Olmesartan medoxomil?+?amlodipine?+?HCTZ was generally well tolerated in the TRINITY study, with adverse events usually being mild or moderate in severity.     

奥美沙坦酯治疗原发性高血压的疗效和安全性

目的：评价奥美沙坦酯治疗原发性高血压的疗效和安全性。方法：选择轻、中度高血压患者64例，随机分为奥美沙坦酯治疗组（n=34例）和缬沙坦对照组（n=30例），每日1次口服奥美沙坦酯20mg或缬沙坦80mg，2周后如舒张压≥90mmHg，则剂量加倍，进行8周的临床观察。结果：两组患者血压均得到明显降低（P〈0．01），奥关沙坦酯组，总有效率88．2％；缬沙坦组总有效率86．7％。两组比较无统计学差异（P〉0．05）。结论：奥美沙坦酯治疗原发性高血压疗效显著，与进口同类药缬沙坦相当，不良反应少，安全有效。     

Olmesartan medoxomil: a review of its use in the management of hypertension

Olmesartan medoxomil (Olmetec, Benicar) is an angiotensin II type 1 (AT(1)) receptor antagonist (angiotensin receptor blocker [ARB]) that inhibits the actions of angiotensin II on the renin-angiotensin-aldosterone system, which plays a key role in the pathogenesis of hypertension. Oral olmesartan medoxomil 10-40 mg once daily is recommended for the treatment of adult patients with hypertension. In those with inadequate BP control using monotherapy, fixed-dose olmesartan medoxomil/hydrochlorothiazide (HCTZ) [Olmetec plus, Benicar-HCT] combination therapy may be initiated. Extensive clinical evidence from several large well designed trials and the clinical practice setting has confirmed the antihypertensive efficacy and good tolerability profile of oral olmesartan medoxomil, as monotherapy or in combination with HCTZ, in patients with hypertension, including elderly patients with isolated systolic hypertension (ISH). Notably, BP control is sustained throughout the 24-hour dosage interval, including during the last 4 hours of this period. In clinical trials, olmesartan medoxomil monotherapy provided better antihypertensive efficacy than losartan, candesartan cilexetil or irbesartan monotherapy, and was at least as effective as valsartan treatment, with a faster onset of action than other ARBs in terms of reductions from baseline in diastolic BP (DBP) and, in most instances, systolic BP (SBP). Combination therapy with olmesartan medoxomil plus HCTZ was superior to that with benazepril plus amlodipine, as effective as that with losartan plus HCTZ, noninferior to that with atenolol plus HCTZ, but less effective than that with telmisartan plus HCTZ, in individual trials. Data from ongoing clinical outcome trials are required to more fully determine the relative position of olmesartan medoxomil therapy in the management of hypertension. In the meantime, the consistent antihypertensive efficacy during the entire 24-hour dosage interval and good tolerability profile of olmesartan medoxomil, with or without HCTZ, make it a valuable option for the treatment of adult patients with hypertension, including the elderly.     

Olmesartan medoxomil combined with hydrochlorothiazide improves 24-hour blood pressure control in moderate-to-severe hypertension

Abstract

Background:

Twenty-four-hour ambulatory blood pressure monitoring (ABPM) has been shown to be more reliable than conventional measurements for hypertension assessment and the associated increased risk of cardiovascular events. Olmesartan/hydrochlorothiazide combination therapy has demonstrated increased blood pressure lowering over 24 hours compared with the component monotherapies. This prespecified pooled analysis of data from two trials investigated the effects of olmesartan/hydrochlorothiazide combination therapy and olmesartan monotherapy on 24-hour blood pressure control in patients with moderate-to-severe hypertension.     

Olmesartan medoxomil self-microemulsifying drug delivery system reverses apoptosis and improves cell adhesion in trinitrobenzene sulfonic acid-induced colitis in rats

Olmesartan medoxomil (OM) is an angiotensin receptor blocker. This study aimed to investigate the effects of OM self-microemulsifying drug delivery system (OMS) in trinitrobenzene sulfonic acid (TNBS)-induced acute colitis in rats. Besides two control groups, five TNBS-colitic-treated groups (n = 8) were given orally sulfasalazine (100 mg/kg/day), low and high doses of OM (3.0 and 10.0 mg/kg/day) (OML and OMH) and of OMS (OMSL and OMSH) for seven days. A colitis activity score was calculated. The colon was examined macroscopically. Colonic levels of myeloperoxidase, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), malondialdehyde, and reduced glutathione were measured. Plasma and colonic olmesartan levels were measured. Colonic sections were subjected to hematoxylin and eosin staining and immunohistochemical staining for E-cadherin, caspase-3, and matrix metalloproteinase-9 (MMP-9). Protein expression of E-cadherin, Bcl-2 associated X protein (Bax), and B-cell lymphoma 2 (Bcl-2), and cleaved caspase-3 by Western blot was done. TNBS-colitic rats showed increased colonic myeloperoxidase, TNF-α, IL-6, and malondialdehyde, decreased colonic glutathione, histopathological, immunohistochemical, and protein expression alterations. OMS, compared with OM, dose-dependently achieved higher colonic free olmesartan concentration, showed better anti-inflammatory, antioxidant, and anti-apoptotic effects, improved intestinal barrier, and decreased mucolytic activity. OMS more effectively up-regulated the reduced Bcl-2, Bcl-2/Bax ratio, and E-cadherin expression, and down-regulated the overexpressed Bax, cleaved caspase-3, and MMP-9. OMSL exerted effects comparable to OMH. Sulfasalazine exerted maximal colonic protective effects and almost completely reversed colonic damage, and OMSH showed nearly similar effects with non-significant differences in-between or compared with the normal control group. In conclusion, OMS could be a potential additive treatment for Crohn''s disease colitis.     

奥美沙坦

奥美沙坦由ForestLaboratOrieS公司开发，为血管紧张素，受体阻断剂（A日B），通过选择性作用于血管平滑肌，阻断血管紧张素11与血管平滑肌中AT，受体的结合，其对A下、受体的亲和力是其对AT2受体的12500倍。     

奥美沙坦酯与吲哒帕胺联合治疗原发性高血压的疗效及安全性研究

目的观察奥美沙坦酯与吲哒帕胺联合治疗原发性高血压的疗效及安全性。方法将160名原发性高血压患者随机分为奥美沙坦酯组与贝那普利组,每组各80例,患者每天早晨分别顿服奥美沙坦酯2．5mg和吲哒帕胺2．5mg,或贝那普利10mg和吲哒帕胺2．5mg,疗程为8周,观察治疗前后临床疗效及不良反应发生情况。结果治疗后两组患者血压有明显下降,奥美沙坦酯组收缩压与舒张压分别从治疗前（168．9±4．1）mmHg、（100．4±7．2）mmHg降至（125．9±8．9）mmHg、（80．9±6．6）mmHg（P〈0．05）,8周后有效率达92．5％;贝那普利组收缩压与舒张压分别从治疗前（170．4±15．1）mmHg、（102．9±7．7）mmHg降至（128．9±8．2）mmHg、（81．4±9．1）mmHg（P〈0．05）,8周后有效率达90．o％。两组患者均未发生严重不良事件,安全性指标无异常。结论联用奥美沙坦酯与吲哒帕胺治疗原发性高血压安全有效,副作用少,是高血压治疗联合用药的理想组合,可推荐临床应用。     

阿奇沙坦酯

阿奇沙坦酯(azilsartan medoxomil)是日本武田(Takeda)制药公司开发的一种新型血管紧张素Ⅱ受体阻滞剂,于2011年2月获美国FDA批准上市,商品名为Edabi。     

Olmesartan medoxomil, a newly developed angiotensin II type 1 receptor antagonist, protects against renal damage in advanced glycation end product (age)-injected rats

Diabetic nephropathy is a leading cause of end-stage renal disease in industrialized countries. Although the molecular mechanisms for the development and progression of diabetic nephropathy are not fully understood, the formation of advanced glycation end products (AGEs) and activation of the renin-angiotensin system (RAS) have been considered to be the main factors participating in the pathogenesis of diabetic nephropathy. However, functional cross-talk between AGEs and the RAS remains to be elucidated. In this study, we examined the effects of oral administration of olmesartan medoxomil, a newly developed angiotensin II type 1 receptor antagonist, on renal damage in AGE-treated rats. Administration of olmesartan medoxomil significantly inhibited the increase of systolic and diastolic blood pressure levels and urinary N-acetyl-beta-D-glucosaminidase activity in exogenously AGE-injected rats. Furthermore, olmesartan medoxomil treatment also prevented glomerulosclerosis in AGE-treated rats. These results indicate that exogenous AGE treatment could induce renal damage via the activation of the RAS. Our study suggests that olmesartan medoxomil could be a valuable drug for the treatment of diabetic nephropathy by blocking the deleterious effects of AGEs.     

Olmesartan: Induced maculopapular rash

Olmesartan medoxomil is an angiotensin receptor blocker (ARB) which is shown to be effective and well tolerated in hypertensive patients. It is a frequently prescribed antihypertensive as it is considered safe. Here, we report the case of a patient who developed maculopapular rash during the course of the treatment with olmesartan medoxomil.KEY WORDS: Angiotensin receptor blockers, maculopapular rash, olmesartan     

奥美沙坦酯合成路线图解

奥美沙坦酯(olmesartan medoxomil,1),化学名为4-(1-羟基-1-甲基乙基)-2-丙基-1-[[2'-(1H-四唑-5-基)联苯-4-基]甲基]咪唑-5-羧酸(5-甲基-2-氧代-1,3-二氧杂环戊烯-4-基)甲基酯,是由日本Sankyo公司研发的一种AT_1受体拮抗剂,2002年5月美国FDA批准用于治疗高血压.本品对不同程度的高血压降压作用均较好,患者耐受性好.     

奥美沙坦酯的工艺改进

目的 改进奥美沙坦酯的合成工艺。方法 以2-氰基-4''-甲基联苯(2)为起始原料,经溴代反应,“一锅法”完成N-烷基化和皂化-酯化反应,再经氰基四氮唑化反应,得到奥美沙坦酯(1)。结果 3步得到成品,总收率46.5%(以2-氰基-4''-甲基联苯计)。结论 改进后的工艺非常实用,适合工业化生产。     

高效液相色谱法测定奥美沙坦酯片的含量

目的：建立高效液相色谱法测定奥美沙坦酯片的含量。方法：采用C18色谱柱,乙腈-10mmol/L磷酸二氢钾缓冲液（0.2%三乙胺,用磷酸调节pH至3.0）（45：55）为流动相,检测波长为256nm。结果：奥美沙坦酯浓度在10.8～86.4μg/ml范围内线性关系良好（r=0.9999）,平均回收率为：100.75%（RSD=0.61%）。结论：该方法简单、准确,适用于奥美沙坦酯片的含量测定。     

奥美沙坦酯胶囊的人体药动学及生物等效性

目的：研究奥美沙坦酯胶囊与片剂的人体药动学及相对生物利用度.方法：18名健康志愿受试者采用随机交叉试验设计,分别口服受试制剂（奥美沙坦酯胶囊）和参比制剂（奥美沙坦酯片）20 mg,服药后0.5～36 h内间隔采血,采用固相萃取结合HPLC-MS/MS法,比较两者的生物利用度.结果：奥美沙坦酯胶囊与片剂的主要药动学参数：Cmax分别为（530±180）μg·L^-1和（660±240）μg·L^-1;tmax分别为（3.1±0.8）h和（2.4±0.7）h;AUC0-36h分别为（4 200±1 700）h·μg·L^-1和（4 400±1 400）h·μg·L^-1;t1/2分别为（6.7±1.1）h和（6.7±0.9）h;以AUC0-36 h计算,奥美沙坦酯胶囊的相对生物利用度为（95.6±22.4）%.结论：奥美沙坦酯胶囊与片剂具有生物等效性.     

Azilsartan medoxomil for the treatment of hypertension

The use of angiotensin receptor blockers (ARBs) represents a favorable approach for the control of blood pressure in patients with hypertension. Azilsartan medoxomil, a prodrug that undergoes rapid hydrolysis to its active moiety azilsartan, is an angiotensin AT(1) receptor antagonist with promising antihypertensive activity and a good safety profile. The agent has been evaluated as monotherapy and in combination with amlodipine or chlorthalidone in phase III trials in patients with essential hypertension. In 2011, azilsartan medoxomil was approved in the U.S. for the treatment of hypertension.