肾素抑制剂阿利克仑的药理与临床评价

阿利克仑是一种有效的肾素抑制剂,它比早期的肾素抑制剂口服吸收更好,而且半衰期很长,每日1次即可,是一种很有前途的新型降压药。长期数据还未公布。现对其药理作用、药动学、临床疗效及安全性等做一综述。     

新颖抗高血压药物——口服肾素抑制剂阿利克仑

肾素-血管紧张素-醛固酮系统（RAAS）作为心功能的主要调节者，其重要作用已自拮抗这一系统的药物如血管紧张素转化酶（ACE）抑制剂、血管紧张素受体阻滞剂（ARB）和醛固酮拮抗剂在目前心血管疾病管理中的地位而得到相当佐证。大量临床研究业经确认，醛固酮拮抗剂、     

抗高血压药物阿利克仑的合成研究

目的 研究抗高血压药阿利克仑的化学合成方法。方法 以光学纯中间体(3S,5S,1′S,3′S)-5-(1′-叠氮基-3′-羟甲基-4′-甲基戊基)-3-异丙基二氢呋喃-2-酮为起始原料,经氧化、亲核加成、氢化、Boc 保护、氨解、脱保护等反应得到阿利克仑游离碱。结果与结论 以总收率 35.7 % 合成阿利克仑。该合成路线反应步骤简短,操作简便,收率高,反应条件温和,适合工业化生产。     

新型抗高血压药阿利吉仑的心肾保护作用研究进展

目的:介绍阿利吉仑心肾保护作用的研究进展。方法:根据文献,综述阿利吉仑在降压治疗过程中产生的心肾保护作用。结果:阿利吉仑通过直接抑制肾素发挥治疗作用的同时,可减轻高血压患者的左心室肥厚,降低心衰患者的脑利钠肽水平,减少或减轻蛋白尿的产生。结论:阿利吉仑在发挥药效的过程中对心肾具有保护作用,有可能成为心血管系统疾病、糖尿病伴肾病的高血压患者的首选药。     

口服抗高血压药的利用调查与分析

目的 了解某医院口服抗高血压药的使用情况，提高该类药物的用药合理性。方法 查阅本院2003年1～6月份心血管内科门诊处方，对使用口服抗血压药的处方采用DDDs分析方法和药物经济学方法进行统计分析，以调查口服抗血压药的利用情况及用药特点。结果 在用药品种上钙离子拮抗剂出现的频率最大，单个药品中非洛地平、氨氯地平、美托洛尔使用频次最多，占主要地位，其次是吲哒帕胺。结论 该院口服抗高血压药的利用基本合理。开发国产的新型长效口服抗高压药是防治高血压病的需求。     

口服抗高血压药临床应用分析

目的：了解河北医科大学第三医院口服抗高血压药（化学药部分）的使用情况,为临床合理用药提供参考。方法：对我院2005—2009年口服抗高血压药的种类、用量、销售金额、用药频度等进行统计分析。结果：5年来,我院抗高血压药的销售金额、用药频度增长迅速,钙通道阻滞剂（CCB）类药物用量排在首位,其次是血管紧张素Ⅱ受体拮抗剂（ARB）和血管紧张素转换酶抑制剂（ACEI）类。价格适宜的普萘洛尔和复方利血平氨氯喋啶等药物DDDs值排序靠前。结论：我院抗高血压药应用结构基本合理。     

口服抗高血压药应用分析

目的评价抗高血压药使用情况。方法采用WHO推荐的限定日剂量法,对本院2009年8月门诊处方抗高血压药的使用情况进行统计。结果钙离子通道颉颃药（CCB）、血管紧张素Ⅱ受体颉颃药（ARB）的使用频率最高。联合用药占全部处方的32.37%,其中两药联用为主,占29.61%。结论本院抗高血压药应用基本符合2005年版《中国高血压防治指南》。单药治疗以第三代钙离子通道颉颃药和血管紧张素Ⅱ受体颉颃药（ARB）为主,新型高选择性β受体阻滞药和ACEI也占重要地位。大部分联合用药方案较合理,但缺乏对联合用药提高血压达标率的认识。处方中存在个别重复用药行为应引起临床的重视。     

抗高血压药的临床合理应用

临床上控制高血压愈来愈受到重视，高血压的治疗目标不仅要降低血压，减轻症状，更重要的是预防或缓解左心室重塑、缓解动脉硬化的发展，保护肾功，预防脑卒中、心肌梗死、心衰和猝死的发生，从而降低住院率和死亡率，提高患者的生命质量。如何围绕上述目标合理选用降压药是一个重要的课题。     

门诊口服抗高血压药合理应用分析

目的：通过对门诊口服抗高血压药应用情况,为临床合理治疗高血压提供依据。方法回顾性分析我院2010年9月～2011年9月门诊开出的抗高血压药物的4728例处方,对其药物种类、药物剂量及用药情况进行统计分析。结果我院常用降压药物使用频率从高到低的依次是钙拮抗剂、血管紧张素Ⅱ受体拮抗剂、β受体阻滞剂、血管紧张素转化酶抑制剂及利尿剂。结论我院门诊在降压药物应用基本合理,无滥用药物现象,门诊在联合用药多于单一用药,对于药物之间的相互作用应加强监护。     

抗高血压药研究进展

高血压的发病率越来越高，被认为是当今世界上危害人类健康和导致死亡的主要原因之一。抗高血压药更新换代速度较快，在原有药物的基础上，越来越多的抗高血压药物被应用于临床。该文综述了抗高血压药的研究进展，以期对抗高血压药的临床应用及科研工作提供指导。     

直接肾素抑制剂阿利吉仑治疗高血压病的研究进展

阿利吉仑是第一个用于临床的口服直接肾素抑制剂。临床试验表明,其降压效果与氯沙坦、厄贝沙坦、赖诺普利、雷米普利等一线降压药相当,与血管紧张素转化酶抑制药（ACEI）、血管紧张素Ⅱ受体拮抗药（ARB）、钙通道阻滞药（CCB）或利尿剂等联合使用时降压作用增强。另外,阿利吉仑具有一定的心脏保护作用,且安全性和耐受性良好。本文简要综述了阿利吉仑在治疗高血压病方面的研究进展。     

Effect of the oral renin inhibitor aliskiren on the pharmacokinetics and pharmacodynamics of a single dose of warfarin in healthy subjects

AIMS: To investigate the effects of aliskiren, an oral renin inhibitor, on the pharmacokinetics and pharmacodynamics of warfarin. METHODS: In a single-blind, placebo-controlled, randomized, two-period crossover study, 15 healthy male and female subjects received a single oral dose of 25 mg racemic warfarin twice, once in the morning of the 8th day of treatment with 150 mg aliskiren and once at the same time point during treatment with placebo. Blood samples were collected for the measurement of prothrombin time (PT) and activated thromboplastin time (aPTT) and for determination of plasma concentrations of (R)- and (S)-warfarin. RESULTS: Aliskiren treatment had no effect on the blood coagulation parameters (PT, INR and aPTT). The ratios of least square means (90% CI) of pharmacokinetic parameters in the presence and absence of aliskiren for (R)- and (S)-warfarin were Cmax 0.89 (0.82, 0.96) and 0.88 (0.80, 0.97), AUC(0, infinity) 1.00 (0.94, 1.07) and 1.06 (0.96, 1.16) and t(1/2) 0.99 (0.92, 1.07) and 1.05 (0.96, 1.14). CONCLUSIONS: Multiple doses of aliskiren had no detectable effect on the pharmacokinetics or pharmacodynamics of a single dose of warfarin in healthy subjects.     

肾素抑制剂阿利吉仑治疗高血压的研究进展

肾素抑制剂作用于肾素-血管紧张素系统初始环节,能够有效降低血压、保护靶器官.阿利吉仑是首个成功开发上市的口服肾素抑制剂,其在高血压治疗及靶器官保护方面前景光明.     

The development of the direct renin inhibitor aliskiren: treating hypertension and beyond

Background: Direct renin inhibitors such as aliskiren offer a novel way of treating hypertension and its co-morbidities, conditions with a considerable prevalence, morbidity, and mortality worldwide. Objective: The burden of hypertension worldwide and the role of the renin-angiotensin-aldosterone system in this disease will be reviewed. Current treatments for hypertension and its co-morbidities that work by manipulating this system will be discussed. The development of, and clinical trials involving, direct renin inhibitors will be reviewed, with a focus on aliskiren. Methods: PubMed was utilized to search the most recent literature on the topics of the renin-angiotensin-aldosterone system, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, aldosterone and aliskiren. Results/conclusions: The direct renin inhibitors, including aliskiren, are new agents with great promise for the treatment of hypertension and its co-morbid conditions, including renal and cardiovascular disease.     

Aliskiren,the first in a new class of direct renin inhibitors for hypertension: present and future perspectives

Aliskiren, the direct renin inhibitor, is the first new class of drug available in 13 years for the treatment of hypertension. Renin has long been recognized as a preferred site for blockade of the renin-angiotensin-aldosterone system because it prevents conversion of angiotensinogen to angiotensin I. Aliskiren binds to the active site of the renin molecule, blocking angiotensinogen cleavage, thus, preventing the formation of angiotensin I. Clinical studies have demonstrated at least equivalent or superior blood pressure lowering efficacy compared with existing drugs with a favorable side effect profile. Aliskiren possesses possible synergistic potential when combined with a thiazide diuretic, ACE inhibitor, angiotensin receptor blocker and calcium channel blocker both in terms of efficacy and tolerability. This review aims to define the role of aliskiren in the therapeutic management of hypertension.     

Aliskiren, a novel orally effective renin inhibitor, exhibits similar pharmacokinetics and pharmacodynamics in Japanese and Caucasian subjects

AIMS: Aliskiren is the first in a new class of orally effective renin inhibitors for the treatment of hypertension. This study compared the pharmacokinetic and pharmacodynamic properties of aliskiren in Japanese and Caucasian subjects. METHODS: In this open-label, single-centre, parallel-group, single- and multiple-dose study, 19 Japanese and 19 Caucasian healthy young male subjects received a single 300-mg oral dose of aliskiren on day 1 and then aliskiren 300 mg once daily on days 4-10. Blood samples were collected for the measurement of plasma aliskiren concentration, plasma renin concentration (PRC) and plasma renin activity (PRA). RESULTS: Pharmacokinetic parameters were comparable in Japanese and Caucasian subjects following administration of a single dose of aliskiren {ratio of geometric means: C(max) 1.12 [90% confidence interval (CI) 0.88, 1.43]; AUC(0-72 h) 1.19 [90% CI 1.02, 1.39]} and at steady state [mean ratio: C(max) 1.30 (90% CI 1.00, 1.70); AUC(0-tau) 1.16 (90% CI 0.95, 1.41)]. There was no notable difference in the plasma half-life of aliskiren between Japanese and Caucasian groups (29.7 +/- 10.2 h and 32.0 +/- 6.6 h, respectively). At steady state, peak PRC level and AUC for the concentration-time plot were not significantly different between Japanese and Caucasian subjects (P = 0.64 and P = 0.80, respectively). A single oral dose of aliskiren significantly reduced PRA to a similar extent in Japanese and Caucasian subjects (by 87.5% and 85.7%, respectively, compared with baseline; P < 0.01). Aliskiren was well tolerated by both ethnic groups. CONCLUSIONS: The oral renin inhibitor aliskiren demonstrated similar pharmacokinetic and pharmacodynamic properties in Japanese and Caucasian subjects.     

Protection against tacrolimus-induced cardiotoxicity in rats by olmesartan and aliskiren

Context: Tacrolimus (TAC), a calcineurin inhibitor, is commonly used as an immunosuppressive agent in organ transplantation, but its clinical use may be limited due to cardiotoxicity. Olmesartan (OLM; angiotensin receptor blocker) and aliskiren (ALK; renin inhibitor) may attenuate cardiotoxicity induced by TAC by inhibition of renin–angiotensin aldosterone system.

Objective: The aim of this study was to evaluate the effect of OLM and ALK on TAC-induced cardiotoxicity.

Materials and methods: Male Wistar albino rats weighing 200–250?g (10–12 weeks old) were used in this study. Animals were divided into four groups. Group 1 received normal saline, group 2 received TAC (2?mg/kg, intraperitoneally for 14?d), group 3 received OLM (2?mg/kg, p.o. for 28?d)?+?TAC and group 4 received ALK (50?mg/kg, p.o. for 28?d)?+?TAC. TAC-induced cardiotoxicity was assessed biochemically and histopathologically.

Results: Treatment with OLM or ALK decreased the TAC-induced changes in biochemical markers of cardiotoxicity such as serum aspartate transaminase, creatine kinase and lactate dehydrogenase. OLM or ALK also attenuated the effects of TAC on oxidant–antioxidant parameters such as malondialdehyde, reduced glutathione and catalase. Histopathological and ultrastructural studies showed that OLM or ALK also attenuated TAC-induced cardiotoxicity.

Discussion and conclusion: These results suggest that OLM as well as ALK has protective effects against TAC-induced cardiotoxicity; implying that angiotensin receptor blocker or renin inhibitor, respectively, may counteract cardiotoxicity associated with immunosuppressant use.     

肾素抑制剂阿利吉仑

阿利吉仑(aliskiren)用于肾素-血管紧张素-醛固酮系统(RAAS)的起始步骤达到降压目的,其半衰期极长,耐受性可与安慰剂相媲美。单用阿利吉仑的降压疗效与其他一线降压药相似,甚至更优;联合用药疗效明显提高,不发生有害的药物间相互作用。对于特殊高血压人群如合并糖尿病、肥胖、或是老年高血压病人,阿利吉仑也表现出极好的疗效和耐受性。阿利吉仑对靶器官起到明显的保护作用,可逆转和延缓高血压引起的心血管和肾脏损害。