• 【G2677T/C3435T衍生的ABCB1 (MDR1) 单倍型对氨氯地平在健康受试者中的药代动力学的影响。】 复制标题 收藏 收藏
    DOI:10.1111/j.1365-2125.2006.02733.x 复制DOI
    作者列表:Kim KA,Park PW,Park JY
    BACKGROUND & AIMS: AIM:We aimed to investigate the effect of the ABCB1 gene on the pharmacokinetics of amlodipine. METHODS:Based on polymorphisms of the ABCB1 gene at positions 2677 and 3435, 26 healthy male participants were divided into three groups: subjects with 2677GG/3435CC (n = 9), 2677GT/3435CT (n = 9) and 2677TT/3435TT (n = 8). After a single-dose administration of 5 mg amlodipine, plasma concentrations of amlodipine were measured and its pharmacokinetic characteristics were compared according to ABCB1 genotype. RESULTS:The area under the plasma concentration-time curve was significantly lower in subjects with 2677TT/3435TT (140.8 +/- 35.6 ng h(-1) ml(-1)) and 2677GT/3435CT (149.8 +/- 40.1 ng h(-1) ml(-1)) than in those with 2677GG/3435CC (208.6 +/- 39.2 ng h(-1) ml(-1)) [95% confidence interval (CI) on the difference, 2677GG/3435CC vs. 2677GT/3435CT 12.0, 105.6, P < 0.01; 2677GG/3435CC vs. 2677TT/3435TT 19.6, 116.0, P < 0.01; 2677GT/3435CT vs. 2677TT/3435TT - 39.2, 57.2, P > 0.05]. The peak plasma concentrations were highest in subjects with 2677GG/3435CC (3.8 +/- 0.5 ng ml(-1)), lower in subjects with 2677GT/3435CT (3.2 +/- 0.5 ng ml(-1)) and 2677TT/3435TT (2.7 +/- 0.5 ng ml(-1)) in rank and showed a significant difference between those with 2677GG/3435CC and with 2677TT/3435TT (95% CI on the difference 0.4, 2.0, P < 0.01). However, the oral clearance was higher in subjects with 2677TT/3435TT (37.7 +/- 10.2 l h(-1)) than in those with 2677GT/3435CT (35.7 +/- 9.9 l h(-1)) and with 2677GG/3435CC (24.8 +/- 5.4 l h(-1)) and exhibited a significant difference between ABCB1 genotype groups (95% CI on the difference, 2677GG/3435CC vs. 2677GT/3435CT - 21.5, - 0.3, P < 0.05; 2677GG/3435CC vs. 2677TT/3435TT - 23.8, - 2.0, P < 0.05). CONCLUSION:Amlodipine pharmacokinetics was affected by the genetic polymorphisms of the ABCB1 gene in humans. These findings may provide a plausible explanation for interindividual variation in the disposition of amlodipine, although our study could not explain the exact mechanism(s) by which the polymorphic ABCB1 gene paradoxically reduces the plasma levels of amlodipine. Further evaluation is thus warranted.
    背景与目标:
  • 【氨氯地平和饮食Ca治疗的高血压大鼠的血压和 α-血管反应性。】 复制标题 收藏 收藏
    DOI:10.1016/j.ejphar.2004.02.032 复制DOI
    作者列表:Civantos B,Aleixandre A
    BACKGROUND & AIMS: :It has been suggested that the combination of dietary Ca and Ca2+ channel antagonists could have a synergic antihypertensive effect. In this study, 3-week-old male spontaneously hypertensive rats (SHR) were randomized into four groups of animals. Two of these groups were fed on a normal Ca diet (Ca 1%) and the other two groups were fed on a Ca-enriched diet (Ca 2.5%). One of the groups fed on each diet also received amlodipine (1 mg/kg/day) in their drinking water. Systolic and diastolic arterial blood pressure were measured weekly in the rats, from the 6th week of life until the 25th week of life, by the tail-cuff method, and we also calculated the corresponding pulse pressure values (systolic blood pressure-diastolic blood pressure). Determination of plasma Ca levels by colourimetric methods, and measurement in pithed rats of the pressor responses to the alpha-adrenoceptor agonists methoxamine and B-HT 920 (5-allyl-2-amino-5,6,7,8-tetrahydro-4H-thiazolo-(4,5-d)-acepin-dihydrochloride, talixepole) were also performed using 16- and 23-week-old animals from the different groups. The Ca-enriched diet decreased systolic and diastolic blood pressure in SHR. Almodipine also decreased systolic and diastolic blood pressure in SHR, and this drug intensified the antihypertensive effect of the Ca 2.5% diet in the SHR between weeks 13 and 18. Nevertheless, in the 19- to 25-week-old SHR amlodipine antagonized the effect of dietary Ca on arterial blood pressure. A decrease in the pulse pressure was seen only in the 15- to 20-week-old SHR which had been simultaneously treated with dietary Ca and amlodipine. All the treatments used increased calcaemia, and the highest plasma Ca levels were obtained in the animals which had received the combined treatment with Ca and amlodipine. The responses to methoxamine and to B-HT 920 in the pithed 16-week-old SHR were similar in the four groups of animals. The responses to these agonists in the pithed 23-week-old SHR fed on the Ca-enriched diet were smaller than the corresponding responses in 23-week-old SHR of the untreated group. By contrast, the responses to these agonists were slightly higher in the pithed 23-week-old SHR which were treated with amlodipine than in the pithed 23-week-old SHR in the untreated group. Moreover, amlodipine partially reversed the effect of dietary Ca on alpha-vascular reactivity. According to our results, it would seem inadvisable to use dietary Ca with a Ca2+ channel antagonist with the aim of controlling arterial blood pressure.
    背景与目标: : 有人认为,饮食中的Ca和Ca2通道拮抗剂的组合可能具有协同降压作用。在这项研究中,将3周龄的雄性自发性高血压大鼠 (SHR) 随机分为四组动物。这些组中的两组以正常Ca饮食 (Ca 1%) 喂养,另外两组以富含Ca的饮食 (Ca 2.5%) 喂养。每种饮食喂养的一组还在饮用水中接受氨氯地平 (1 mg/kg/天)。从生命的第6周到生命的第25周,通过尾袖法每周测量大鼠的收缩压和舒张压,我们还计算了相应的脉压值 (收缩压-舒张压)。通过比色法测定血浆Ca水平,并在大鼠中测量对 α-肾上腺素受体激动剂甲氧明和B-HT 920 (5-烯丙基-2-氨基-5,6,7,8-四氢-4h-噻唑-(4,5-d)-乙酰-二盐酸盐,talixepole) 也使用来自不同组的16周和23周大的动物进行。富含Ca的饮食可降低SHR的收缩压和舒张压。Almodipine还降低了SHR的收缩压和舒张压,并且该药物在第13周至第18周之间增强了Ca 2.5% 饮食在SHR中的降压作用。然而,在19至25周龄的SHR氨氯地平拮抗饮食Ca对动脉血压的影响。仅在15至20周龄的SHR中观察到脉压降低,该SHR已同时用饮食中的Ca和氨氯地平治疗。所有使用的治疗都会增加钙血症,并且在接受Ca和氨氯地平联合治疗的动物中获得了最高的血浆Ca水平。在四组动物中,在16周龄的SHR中,对甲氧胺和对b-ht 920的反应相似。在富含Ca的饮食中喂养的23周龄SHR中,对这些激动剂的反应小于未治疗组的23周龄SHR中的相应反应。相比之下,在用氨氯地平治疗的23周龄SHR中,对这些激动剂的反应略高于未治疗组的23周龄SHR。此外,氨氯地平部分逆转了饮食中Ca对 α-血管反应性的影响。根据我们的结果,为了控制动脉血压,将饮食中的Ca与Ca2通道拮抗剂一起使用似乎是不明智的。
  • 【氨氯地平与血管紧张素II受体阻滞剂; 糖尿病患者血压控制评估试验 (ADVANCED-J)。】 复制标题 收藏 收藏
    DOI:10.1186/1471-2261-6-39 复制DOI
    作者列表:Kawamori R,Daida H,Tanaka Y,Miyauchi K,Kitagawa A,Hayashi D,Kishimoto J,Ikeda S,Imai Y,Yamazaki T
    BACKGROUND & AIMS: BACKGROUND:The coexistence of type 2 diabetes mellitus and hypertension increases the risk of cardiovascular diseases. The U.K. Prospective Diabetes Study has shown that blood pressure control as well as blood glucose control is efficient for prevention of complications in hypertensive patients with diabetes mellitus. However, some reports have shown that it is difficult to control the blood pressure and the concomitant use of a plurality of drugs is needed in hypertensive patients with diabetes mellitus. In recent years renin-angiotensin system depressants are increasingly used for the blood pressure control in diabetic patients. Particularly in Japan, angiotensin II (A II) antagonists are increasingly used. However, there is no definite evidence of the point of which is efficient for the control, the increase in dose of A II antagonist or the concomitant use of another drug, in hypertensive patients whose blood pressure levels are inadequately controlled with A II antagonist. METHODS/DESIGN:Hypertensive patients of age 20 years or over with type 2 diabetes mellitus who have been treated by the single use of AII antagonist at usual doses for at least 8 weeks or patients who have been treated by the concomitant use of AII antagonist and an antihypertensive drug other than calcium channel blockers and ACE inhibitors at usual doses for at least 8 weeks are included. DISCUSSION:We designed a multi-center, prospective, randomized, open label, blinded-endpoint trial, ADVANCED-J, to compare the increases in dose of A II antagonist and the concomitant use of a Ca-channel blocker (amlodipine) and A II antagonist in hypertensive patients with diabetes mellitus, whose blood pressure levels were inadequately controlled with A II antagonist. This study is different from the usual previous studies in that home blood pressures are assessed as indicators of evaluation of blood pressure. The ADVANCED-J study may have much influence on selection of antihypertensive drugs for treatment in hypertensive patients with diabetes mellitus. It is expected to give an important hint for considering the validity of selection of antihypertensive drugs from the aspects not only of the antihypertensive effect but medical cost-effectiveness.
    背景与目标:
  • 【氨氯地平联合阿托伐他汀治疗Zucker代谢大鼠颈动脉粥样硬化的联合益处。】 复制标题 收藏 收藏
    DOI:10.1179/1743132812Y.0000000131 复制DOI
    作者列表:Kawai H,Kurata T,Deguchi K,Deguchi S,Yamashita T,Ohta Y,Omote Y,Kono S,Abe K
    BACKGROUND & AIMS: OBJECTIVES:Obesity is the major risk factor for metabolic syndrome and atherosclerotic cardiocerebrovascular diseases. METHODS:We studied effects of amlodipine, atorvastatin, and their combination on carotid arteriosclerotic processes in a metabolic syndrome model of Zucker fatty rats. Zucker fatty rats were treated with vehicle, amlodipine, atorvastatin, or combination amlodipine plus atorvastatin for 28 days. RESULTS:Compared with the single treatment with amlodipine or atorvastatin, the combination of amlodipine plus atorvastatin treatment prevented arteriosclerotic processes, and induced a strong recovery of Sirtuin1 (Sirt1) expression and a marked reduction in p53, p21, and monocyte chemoattractant protein-1 (MCP-1). DISCUSSION:As Sirt1 is a longevity gene that prevents endothelial atherosclerotic processes, and p53, p21, and MCP-1 play pivotal roles in the initiation and development of atherosclerosis, these data suggest a strong synergistic benefit of combination therapy with amlodipine and atorvastatin for preventing atherosclerotic processes, and potentially reducing the clinical risk of cerebrovascular events in metabolic obesity patients.
    背景与目标:
  • 【氨氯地平在肾功能损害中的药代动力学。】 复制标题 收藏 收藏
    DOI:10.1097/00005344-198812007-00013 复制DOI
    作者列表:Laher MS,Kelly JG,Doyle GD,Carmody M,Donohoe JF,Greb H,Volz M
    BACKGROUND & AIMS: :The pharmacokinetics of amlodipine was studied in 27 subjects with renal function ranging from normal to dialysis-dependent. Amlodipine (as a single 5-mg capsule) was administered once daily for 14 days and its plasma concentrations were measured by gas chromatography during and after treatment. Renal impairment had little or no effect on the pharmacokinetics of amlodipine. The elimination half-life was of the order of 50 h, similar to previously observed values, and did not vary with differences in renal function. Steady-state predose concentrations were observed after the ninth dose. Accumulation of amlodipine to steady-state levels was not significantly different from that expected on theoretical grounds and did not significantly change with renal function. These results suggest that once-daily administration of amlodipine is suitable for all degrees of renal function and that dosage adjustment is not necessary in renal impairment.
    背景与目标: : 在27名肾功能从正常到透析依赖的受试者中研究了氨氯地平的药代动力学。每天给药一次氨氯地平 (作为单个5 mg胶囊),持续14天,并在治疗期间和治疗后通过气相色谱法测量其血浆浓度。肾功能损害对氨氯地平的药代动力学几乎没有影响。消除半衰期约为50小时,与先前观察到的值相似,并且没有随肾功能的差异而变化。第9次给药后观察到稳态给药前浓度。氨氯地平积累到稳态水平与理论上的预期无显着差异,并且随肾功能无显着变化。这些结果表明,每天一次氨氯地平适用于所有程度的肾功能,并且在肾功能不全时无需调整剂量。
  • 【缺氧大鼠的肺血管重塑: 氨氯地平,单独和培哚普利的作用。】 复制标题 收藏 收藏
    DOI:10.1016/s0014-2999(01)00855-x 复制DOI
    作者列表:Jeffery TK,Wanstall JC
    BACKGROUND & AIMS: :This study investigated whether pulmonary vascular remodelling in hypoxic pulmonary hypertensive rats (10% oxygen; 4 weeks) could be prevented by treatment, during hypoxia, with amlodipine (10 mg/kg/day, p.o.), either alone or in combination with the angiotensin converting enzyme inhibitor, perindopril (30 mg/kg/day, p.o.). Medial thickening of pulmonary arteries (30-500 microm o.d.) was attenuated by amlodipine whereas it was totally prevented by the combination treatment (amlodipine plus perindopril); neomuscularisation of small alveolar arteries (assessed from critical closing pressure in isolated perfused lungs) was not affected. Pulmonary vascular resistance (isolated perfused lungs) was reduced by both treatment regimes but only combination treatment reduced right ventricular hypertrophy. Thus, amlodipine has anti-remodelling properties in pulmonary hypertensive rats. The finding that combining amlodipine with another anti-remodelling drug produced effects on vascular structure that were additive raises the question of whether combination therapy with two different anti-remodelling drugs may be of value in the treatment of patients with hypoxic (and possibly other forms of) pulmonary hypertension.
    背景与目标: : 这项研究调查了在缺氧期间,单独或联合使用氨氯地平 (10 mg/kg/天,p.o.) 是否可以预防低氧性肺动脉高压大鼠 (10% 氧气; 4周) 的肺血管重塑。血管紧张素转化酶抑制剂,培哚普利 (30 mg/kg/天,p.o.)。氨氯地平可减轻肺动脉内侧增厚 (30-500 microm o.d.),而联合治疗 (氨氯地平加培哚普利) 可完全预防; 小肺泡动脉的新血管形成 (根据孤立的灌注肺中的临界闭合压力评估) 不受影响。两种治疗方案均降低了肺血管阻力 (孤立的灌注肺),但仅联合治疗可降低右心室肥大。因此,氨氯地平在肺动脉高压大鼠中具有抗重塑特性。氨氯地平与另一种抗重塑药物联合使用对血管结构产生累加作用的发现提出了一个问题,即与两种不同的抗重塑药物联合治疗在治疗低氧 (可能还有其他形式) 的患者中是否有价值肺动脉高压。
  • 【氨氯地平和拉西地平对大鼠卵巢切除引起的骨丢失的保护作用。】 复制标题 收藏 收藏
    DOI:10.1016/j.ejphar.2007.09.027 复制DOI
    作者列表:Halici Z,Borekci B,Ozdemir Y,Cadirci E,Suleyman H
    BACKGROUND & AIMS: :Bone is a dynamic organ system that is directly related to calcium and phosphor metabolism. Imbalance in these two parameters upon aging or menopause leads to osteoporosis. Recently, it was also shown by researchers that high blood pressure in elderly women is statistically associated with decreased bone mineral content at the femoral neck, which may increase the susceptibility to fractures. The aim of our study was to investigate the effects of different doses of amlodipine and lacidipine on ovariectomized rat femurs' calcium and phosphor content. Bone calcium and phosphor concentration was measured by a Wavelength Dispersive Spectrometer. Calcium contents of the rat femurs were significantly lower in the ovariectomized group than in the sham group eight weeks after the operation. Amlodipine treatment at doses of 1 and 3 mg/kg significantly increased the calcium (P<0.01) and phosphor concentrations (P<0.01) in the femurs of ovariectomized rats, compared to those of control (ovariectomized) group. Both doses of lacidipine (1 and 3 mg/kg) also effectively increased calcium concentrations (P<0.01) significantly in ovariectomized rats. On the other hand amlodipine treatment at doses of 1 and 3 mg/kg significantly increased the calcium (P<0.01) and phosphor concentrations (P<0.01) in the femurs of ovariectomized rats compared with those of the sham group. In conclusion, amlodipine and lacidipine improved the bone loss in an ovariectomy induced osteopenic rat model. Our findings suggest that potent calcium channel blockers such as amlodipine and lacidipine have a beneficial effect on bone metabolism, and an antihypertensive effect.
    背景与目标: : 骨骼是与钙和磷代谢直接相关的动态器官系统。衰老或更年期时,这两个参数的不平衡会导致骨质疏松症。最近,研究人员还发现,老年妇女的高血压与股骨颈骨矿物质含量降低在统计学上相关,这可能会增加骨折的敏感性。我们研究的目的是研究不同剂量的氨氯地平和拉西地平对去卵巢大鼠股骨钙和磷含量的影响。通过波长色散光谱仪测量骨钙和磷的浓度。术后8周,去卵巢组大鼠股骨的钙含量明显低于假手术组。与对照组 (卵巢切除组) 相比,1和3 mg/kg剂量的氨氯地平处理可显着增加去卵巢大鼠股骨中的钙 (P<0.01) 和磷浓度 (P<0.01)。两种剂量的拉西地平 (1和3 mg/kg) 也有效地增加了去卵巢大鼠的钙浓度 (P<0.01)。另一方面,与假手术组相比,1和3 mg/kg剂量的氨氯地平治疗可显着增加去卵巢大鼠股骨中的钙 (P<0.01) 和磷浓度 (P<0.01)。总之,氨氯地平和拉西地平改善了卵巢切除术诱导的骨质减少大鼠模型的骨丢失。我们的发现表明,有效的钙通道阻滞剂 (例如氨氯地平和拉西地平) 对骨代谢具有有益作用,并具有抗高血压作用。
  • 【氨氯地平和阿托伐他汀的固定剂量组合可改善合并高血压和血脂异常患者的临床结局。】 复制标题 收藏 收藏
    DOI:10.1111/jch.14016 复制DOI
    作者列表:Lin CP,Tung YC,Hsiao FC,Yang CH,Kao YW,Lin YS,Chu YC,Chu PH
    BACKGROUND & AIMS: :Hypertension and dyslipidemia are important risk factors for cardiovascular disease. However, the clinical outcomes of fixed-dose combination (FDC) versus free-equivalent combination (FEC) of amlodipine and atorvastatin in the treatment of concurrent hypertension and dyslipidemia remain unknown. In this study, we included patients with newly diagnosed hypertension and dyslipidemia, without previously established cardiovascular disease, and treated with either FDC or FEC of amlodipine and atorvastatin were identified from the National Health Insurance Research Database of Taiwan and follow-up for 5 years. By using 1:1 propensity score matching, a total of 1756 patients were enrolled in this study. The composite of major adverse cardiovascular events, including all-cause mortality, myocardial infarction (MI), stroke, and coronary revascularization, occurred more frequently in the FEC group than in the FDC group (hazard ratio, 1.88; 95% confidence interval [CI], 1.42 to 2.5). Although the all-cause mortality did not differ (hazard ratio, 0.46; 95% CI, 0.36 to 1.59), the FEC group developed increased MI, stroke, and coronary revascularization (hazard ratio, 2.87; 95% CI, 1.07 to 7.68; hazard ratio, 1.97; 95% CI, 1.41 to 2.74; and hazard ratio, 2.44; 95% CI, 1.26 to 4.69, respectively). Furthermore, as an unexpected result, a higher risk to develop new-onset diabetes mellitus was observed with FEC regimens (hazard ratio, 2.19; 95% CI, 1.6 to 3.0). In conclusion, although the all-cause mortality did not differ between the two groups, the FDC regimen of amlodipine and atorvastatin improved clinical outcomes when compared to FEC in patients with newly diagnosed hypertension and dyslipidemia.
    背景与目标: : 高血压和血脂异常是心血管疾病的重要危险因素。然而,氨氯地平和阿托伐他汀的固定剂量组合 (FDC) 与自由等效组合 (FEC) 治疗并发高血压和血脂异常的临床结果仍然未知。在这项研究中,我们从台湾国家健康保险研究数据库中确定了新诊断的高血压和血脂异常,没有先前确定的心血管疾病,并接受了FDC或氨氯地平和阿托伐他汀的FEC治疗,并进行了5年的随访。通过使用1:1倾向评分匹配,本研究共招募了1756名患者。与FDC组相比,FEC组的主要不良心血管事件 (包括全因死亡率,心肌梗死 (MI),卒中和冠状动脉血运重建) 的发生率更高 (风险比,1.88; 95% 置信区间 [CI],1.42至2.5)。尽管全因死亡率没有差异 (风险比,0.46; 95% CI,0.36至1.59),但FEC组出现了MI,中风和冠状动脉血运重建 (风险比,2.87; 95% CI,1.07至7.68; 风险比,1.97; 95% CI,1.41至2.74; 和危险比,2.44; 95% CI,分别为1.26至4.69)。此外,作为意外的结果,使用FEC方案观察到发生新发糖尿病的较高风险 (风险比,2.19; 95% CI,1.6至3.0)。总之,尽管两组的全因死亡率没有差异,但与FEC相比,氨氯地平和阿托伐他汀的FDC方案在新诊断的高血压和血脂异常患者中改善了临床结局。
  • 【口服直接肾素抑制剂阿利吉仑作为附加疗法对氨氯地平单药治疗无反应的患者的抗高血压疗效。】 复制标题 收藏 收藏
    DOI:10.1111/j.1524-6175.2007.06614.x 复制DOI
    作者列表:Drummond W,Munger MA,Rafique Essop M,Maboudian M,Khan M,Keefe DL
    BACKGROUND & AIMS: :This study investigated the addition of the direct renin inhibitor aliskiren to amlodipine in patients with mild to moderate hypertension that was inadequately controlled with amlodipine alone. Following once-daily treatment with amlodipine 5 mg for 4 weeks, patients whose hypertension responded inadequately to therapy (mean sitting diastolic blood pressure [DBP] 90-109 mm Hg) (n=545) were randomized to 6 weeks of double-blind treatment with amlodipine 5 mg plus aliskiren 150 mg, amlodipine 5 mg, or amlodipine 10 mg. At the study's end, mean systolic blood pressure and DBP reductions with the combination of aliskiren 150 mg and amlodipine 5 mg (11.0/8.5 mm Hg) were significantly greater (P<.0001) than with amlodipine 5 mg (5.0/4.8 mm Hg)--the comparator group--but similar to amlodipine 10 mg (9.6/8.0 mm Hg). All treatments were well tolerated. Edema occurred more frequently with amlodipine 10 mg (11.2%) than with combination therapy (2.1%) or amlodipine 5 mg (3.4%). In conclusion, aliskiren 150 mg plus amlodipine 5 mg shows similar but not better blood pressure-lowering efficacy when compared with amlodipine 10 mg in patients not completely responsive to amlodipine 5 mg; less edema was noted with combination therapy.
    背景与目标: : 这项研究调查了单独使用氨氯地平无法充分控制的轻度至中度高血压患者在氨氯地平中添加直接肾素抑制剂阿利吉仑的情况。每天用氨氯地平5 mg治疗4周后,高血压对治疗反应不充分的患者 (平均舒张压 [DBP] 90-109毫米Hg) (n = 545) 被随机分配到6周的双盲治疗氨氯地平5 mg加阿利吉仑150 mg,氨氯地平5 mg,或氨氯地平10 mg。在研究结束时,阿利吉仑150 mg和氨氯地平5 mg (11.0/8.5毫米Hg) 联合使用的平均收缩压和DBP降低显着高于 (P<.0001) 氨氯地平5 mg (5.0/4.8毫米Hg) (比较组)-但与氨氯地平10 mg (9.6/8.0毫米Hg) 相似。所有治疗均具有良好的耐受性。与联合治疗 (2.1%) 或氨氯地平5 mg (3.4%) 相比,氨氯地平10 mg (11.2%) 发生水肿的频率更高。总之,在对氨氯地平5 mg无完全反应的患者中,与氨氯地平10 mg相比,阿利吉仑150 mg加氨氯地平5 mg显示出相似但更好的降血压效果; 联合治疗可减少水肿。
  • 【氨氯地平通过Akt-1-dependent方式保护大鼠心室成肌细胞H9c2免受缺氧诱导的细胞凋亡并恢复氧化平衡。】 复制标题 收藏 收藏
    DOI:10.1097/FJC.0000000000000130 复制DOI
    作者列表:Nehra S,Bhardwaj V,Saraswat D
    BACKGROUND & AIMS: BACKGROUND:Hypoxia-induced rise in intracellular calcium concentration is a causative agent of apoptosis and oxidative damage in cardiomyocytes. We examined the efficacy of calcium channel blocker amlodipine in preventing hypoxia-induced apoptosis in H9c2 cells and restoring oxidative balance. METHODS:H9c2 cells were exposed to hypoxia (0.5% oxygen) to evaluate the efficacy of amlodipine in restoring cellular calcium levels. Cellular markers of apoptosis (Bax/Bcl2 and caspase-3, -7, and -9) and pro-survival markers (Akt/p-Akt levels) were evaluated under hypoxia. Redox damage was evaluated by assessing markers of oxidative damage, that is, glutathione reduced, glutathione oxidized, lipid peroxidation, reactive oxygen species, and manganese superoxide dismutase activity. Cellular adenosine triphosphate (ATP) pool and AMPKα levels were measured to evaluate regulation of metabolism under hypoxia. RESULTS:Amlodipine treatment at 25 nM prevented apoptosis and restored cellular calcium levels and oxidative damage in cardiomyocytes. Stabilization of caspase-3, -7, and -9 along with restoration of Akt/p-Akt levels depicted pro-survival efficacy of amlodipine. Also, restoration of cellular ATP and AMPKα levels indicates that amlodipine prevents cardiomyocytes from hypoxia-induced metabolic stress. CONCLUSIONS:Amlodipine thus protects H9c2 cells from hypoxia-induced apoptosis by regulating Akt/p-Akt-mediated caspase-3, -7, and -9 activation and restoring cellular ATP and redox status.
    背景与目标:
  • 【苯磺酸氨氯地平与坎地沙坦酯在高血压患者中的比较-办公室和自我测量血压: 一项随机,双盲,比较,多中心试验。】 复制标题 收藏 收藏
    DOI:10.2165/00044011-200525090-00002 复制DOI
    作者列表:Trenkwalder P,Regourd E,Kluth-Pepper B,Sauerbrey-Wullkopf N
    BACKGROUND & AIMS: OBJECTIVE:The aim of this study was to compare the antihypertensive efficacy and tolerability of the calcium channel antagonist amlodipine besylate versus the angiotensin II type 1 receptor antagonist candesartan cilexetil in hypertensive patients. PATIENTS AND METHODS:After a 2-week placebo washout period, 326 patients with essential hypertension were randomised to receive amlodipine 5mg once daily or candesartan cilexetil 8mg once daily in a double-blind, parallel-group design with a 12-week active treatment period followed by a 4-day placebo drug-free period. The initial daily dose could be doubled at week 6 if office diastolic blood pressure (DBP) was still >/=90mm Hg. BP changes were assessed daily through patient self-measurements, and fortnightly by office BP measurements. RESULTS:A total of 294 patients (151 amlodipine and 143 candesartan cilexetil) were included in the per-protocol analysis of the primary endpoint of BP change from baseline at 12 weeks. Reductions in sitting office systolic BP (SBP) [amlodipine 24.4mm Hg, candesartan cilexetil 22.3mm Hg] and DBP (amlodipine 14.9mm Hg, candesartan cilexetil 14.8mm Hg) were statistically equivalent within the chosen range of equivalence (5mm Hg for SBP and 3mm Hg for DBP). The proportion of controlled patients (office BP <140/90mm Hg) at the end of therapy was similar in both treatment groups (amlodipine 46.9%, candesartan cilexetil 44.4%). The reduction in self-measured DBP was significantly greater (p < 0.05) for amlodipine (7.2mm Hg) compared with candesartan cilexetil (4.8mm Hg). There was no significant difference between the two treatments in the incidence of adverse events reported. CONCLUSIONS:Amlodipine besylate and candesartan cilexetil were both very effective in lowering office BP after 12 weeks of treatment. There was a trend towards a better self-measured BP reduction with amlodipine compared with candesartan cilexetil. The overall incidence of adverse events was comparable between the two treatments.
    背景与目标:
  • 【氨氯地平和阿托伐他汀通过调节自发性高血压大鼠核因子 κ B受体激活剂配体/核因子 κ B受体激活剂/骨保护素系统改善高血压心肌肥大。】 复制标题 收藏 收藏
    DOI:10.1177/1535370216630180 复制DOI
    作者列表:Lu J,Liu F,Liu D,Du H,Hao J,Yang X,Cui W
    BACKGROUND & AIMS: :The present study aims to study the role of receptor activator of nuclear factor kappa B ligand/receptor activator of nuclear factor kappa B/osteoprotegerin (RANKL/RANK/OPG) system in cardiac hypertrophy in a spontaneous hypertension rat (SHR) model and the effects of amlodipine and atorvastatin intervention. Thirty-six-week-old male SHRs were randomly divided into four groups: 1) SHR control group; 2) amlodipine alone (10 mg/kg/d) group, 3) atorvastatin alone (10 mg/kg/d) group, 4) combination of amlodinpine and atorvastatin (10 mg/kg/d for each) group. Same gender, weight, and age of Wistar-Kyoto (WKY) rats with normal blood pressure were used as normal control. Drugs were administered by oral gavage over 12 weeks. The thicknesses of left ventricle walls, left ventricle weight, and cardiac function were measured by transthoracic echocardiography. Left ventricular pressure and function were assessed by hemodynamic examination. Cardiomyocyte hypertrophy and collagen accumulation in cardiac tissue were measured by hematoxylin and eosin (HE) and Masson staining, respectively. The hydroxyproline content of cardiac tissue was examined by biochemistry technique. RANKL, RANK and OPG mRNA, protein expression and tissue localization were studied by RT-PCR, Immunohistochemistry and Western blot. Treatment with amlodipine or atorvastatin alone significantly decreased left ventricular mass index, cardiomyocyte cross-sectional area and interstitial fibrosis in SHR (each P < 0.05). Moreover, combined amlodipine and atorvastatin treatment induced significant reversal of left ventricular hypertrophy and decreased cardiomyocyte cross-sectional area and interstitial fibrosis in SHR to a greater extent than each agent alone (P < 0.05). Compared with WKY rats, the myocardial expression of RANKL, RANK, and OPG was increased. Both amlodipine and atorvastatin reduced RANKL, RANK, and OPG expression, with the best effects seen with the combination. Based on our results, activation of the RANKL/RANK/OPG system may be an important factor leading to ventricular remodeling in SHR rats. Amlodipine and atorvastatin could improve ventricular remodeling in SHR rats through intervention with the RANKL/RANK/OPG system.
    背景与目标: 本研究旨在研究核因子 κ B受体激活剂配体/核因子 κ B受体激活剂/骨保护素 (RANKL/RANK/OPG) 系统在自发性高血压大鼠 (SHR) 模型中心肌肥大的作用以及氨氯地平和阿托伐他汀的干预作用。36周龄男性SHR随机分为四组: 1) SHR对照组; 2) 氨氯地平单用 (10  mg/kg/d) 组,3) 阿托伐他汀单用 (10  mg/kg/d) 组,4) 氨氯地平联合阿托伐他汀 (10  mg/kg/d) 组。将血压正常的Wistar-Kyoto (WKY) 大鼠的相同性别,体重和年龄用作正常对照。在12周内通过口服灌胃给药。通过经胸超声心动图测量左心室壁的厚度,左心室重量和心功能。通过血流动力学检查评估左心室压力和功能。分别用苏木精和曙红 (HE) 和Masson染色测量心肌细胞肥大和心肌组织中胶原蛋白的积累。通过生化技术检查心脏组织中的羟脯氨酸含量。通过rt-pcr,免疫组织化学和Western blot研究RANKL,RANK和OPG mRNA,蛋白质表达和组织定位。单独使用氨氯地平或阿托伐他汀可显着降低SHR的左心室质量指数,心肌细胞横截面积和间质纤维化 (各p  <  0.05)。此外,氨氯地平和阿托伐他汀联合治疗可显著逆转SHR的左心室肥厚,降低心肌细胞横截面积和间质纤维化,其程度高于单独治疗 (p  <  0.05)。与WKY大鼠相比,RANKL,RANK和OPG的心肌表达增加。氨氯地平和阿托伐他汀均降低RANKL,RANK和OPG表达,联合使用效果最佳。根据我们的结果,RANKL/RANK/OPG系统的激活可能是导致SHR大鼠心室重构的重要因素。氨氯地平和阿托伐他汀可通过RANKL/RANK/OPG系统干预改善SHR大鼠心室重构。
  • 【通过24小时动态血压监测对每日一次氨氯地平与尼群地平在原发性高血压中的降压效果进行比较评估。】 复制标题 收藏 收藏
    DOI:10.1097/00005344-199310000-00002 复制DOI
    作者列表:Coca A,Picado MJ,De la Sierra A,Aguilera MT,Sánchez M,Lluch MM,Urbano-Márquez A
    BACKGROUND & AIMS: :We compared the antihypertensive efficacy of once-daily amlodipine (AM) versus nitrendipine (NTR) by 24-h ambulatory blood pressure monitoring (24-h ABPM) in 32 patients with mild to moderate essential hypertension (EH). After a 2-week single-blind, placebo run-in period, patients were randomized in a double-blind, parallel fashion: 14 received AM 5 mg and 18 NTR 10 mg. After 2 weeks, dose was adjusted if necessary (AM 10 mg or NTR 20 mg) and continued for another 6-week period. At the end of the placebo period and during the last week of treatment, patients underwent 24-h ABPM. Initial office BP mean values were similar in both groups (169.8 +/- 14/102.5 +/- 6 vs. 167.1 +/- 14/98.7 +/- 5 mm Hg, respectively, p = NS). A comparable decrease in office mean values of systolic BP (SBP, -22.3 +/- 13 vs. -19.1 +/- 16 mm Hg) and diastolic BP (DBP, -12.0 +/- 5 vs. -8.1 +/- 8 mm Hg) was observed. Nevertheless, 24-h ABPM mean values differed significantly between patients treated with AM or NTR with regard to 24-h SBP (120.0 +/- 10 vs. 132.5 +/- 1 mm Hg, p = 0.01). Moreover, the average decrease in 24-h SBP (-19.3 +/- 6 vs. -5.2 +/- 11 mm Hg, p = 0.0036) and 24-h DBP (-10.7 +/- 4 vs. -3.7 +/- 6 mm Hg, p = 0.0047) was higher in the AM group, with no changes in 24-h heart rate (HR). At equivalent once-daily dosage, AM was more effective than NTR in decreasing BP assessed by 24-h ABPM.
    背景与目标: : 我们通过24小时动态血压监测 (24小时ABPM) 比较了32例轻度至中度原发性高血压 (EH) 患者每日一次氨氯地平 (AM) 和尼群地平 (NTR) 的降压疗效。在为期2周的单盲安慰剂磨合期后,患者以双盲,平行方式随机分配: 14例接受AM 5 mg和18 NTR 10 mg。2周后,必要时调整剂量 (AM 10 mg或NTR 20 mg),并持续6周。在安慰剂期结束时以及治疗的最后一周,患者接受了24小时ABPM。两组的初始办公室血压平均值相似 (分别为169.8 +/- 14/102.5 +/- 6对167.1 +/- 14/98.7 +/-5毫米Hg,p = NS)。观察到收缩压 (SBP,-22.3/- 13对-19.1/-16毫米Hg) 和舒张压 (DBP,-12.0/- 5对-8.1/-8毫米Hg) 的办公室平均值相当降低。然而,就24小时SBP而言,接受AM或NTR治疗的患者之间的24小时ABPM平均值存在显着差异 (120.0/- 10对132.5/-1毫米Hg,p = 0.01)。此外,24小时SBP (-19.3 +/- 6对-5.2 +/-11毫米Hg,p = 0.0036) 和24小时DBP (-10.7 +/- 4对-3.7 +/-6毫米Hg) 的平均下降,AM组p = 0.0047) 较高,24小时心率 (HR) 无变化。在同等的每日一次剂量下,AM在降低24小时ABPM评估的BP方面比NTR更有效。
  • 【联合贝那普利-氨氯地平对心脏缺血后心脏一氧化氮,cGMP和TNF-α 产生的有益作用。】 复制标题 收藏 收藏
    DOI:10.1097/01.fjc.0000211750.01326.b3 复制DOI
    作者列表:Siragy HM,Xue C,Webb RL
    BACKGROUND & AIMS: :The aim of this study was to determine if myocardial inflammation is increased after myocardial ischemia and whether angiotensin-converting enzyme inhibitors, calcium channel blockers, or diuretics decrease mediators of inflammation in rats with induced myocardial ischemia. Changes in cardiac interstitial fluid (CIF) levels of nitric oxide metabolites (NOX), cyclic guanosine 3',5'-monophosphate (cGMP), angiotensin II (Ang II), and tumor necrosis factor-alpha (TNF-alpha) were monitored with/without oral administration of benazepril, amlodipine, combined benazepril-amlodipine, or hydrochlorothiazide. Using a microdialysis technique, levels of several mediators of inflammation were measured after sham operation or 30-minute occlusion of the left anterior descending coronary artery. Compared with sham animals, levels of CIF NOX and cGMP were decreased in animals with ischemia (P < 0.001). Benazepril or amlodipine significantly increased NOX levels (P < 0.05 vs. untreated ischemia), but only benazepril significantly increased cGMP (P < 0.05). Combined benazepril-amlodipine further increased CIF NOX and cGMP (P < 0.001), compared with either drug alone. CIF Ang II and TNF-alpha in sham animals did not change significantly. In animals with ischemia, CIF Ang II and TNF-alpha increased progressively. Amlodipine alone, benazepril alone, or combined benazepril-amlodipine significantly reduced TNF-alpha (P < 0.01 for monotherapies and P < 0.001 for combination therapy). Hydrochlorothiazide did not cause significant changes in NOX, cGMP, or TNF-alpha. Combination benazepril-amlodipine may be beneficial for managing cardiac ischemia.
    背景与目标: : 这项研究的目的是确定心肌缺血后心肌炎症是否增加,以及血管紧张素转换酶抑制剂,钙通道阻滞剂或利尿剂是否减少诱发心肌缺血大鼠的炎症介质。监测一氧化氮代谢物 (NOX),环鸟苷3 ',5'-单磷酸 (cGMP),血管紧张素II (Ang II) 和肿瘤坏死因子-α (TNF-α) 的心脏间质液 (CIF) 水平的变化。/不口服贝那普利,氨氯地平,联合贝那普利-氨氯地平,或氢氯噻嗪。使用微透析技术,在假手术或左前降支冠状动脉闭塞30分钟后测量了几种炎症介质的水平。与假动物相比,缺血动物的CIF NOX和cGMP水平降低 (P <0.001)。贝那普利或氨氯地平显著增加NOX水平 (P <0.05与未处理的缺血相比),但只有贝那普利显著增加cGMP (P <0.05)。与单独使用任何一种药物相比,联合贝那普利-氨氯地平进一步增加了CIF NOX和cGMP (P <0.001)。假动物的CIF Ang II和TNF-α 没有明显变化。在缺血动物中,CIF Ang II和TNF-α 逐渐增加。单独使用氨氯地平、单独使用贝那普利或联合使用贝那普利-氨氯地平显著降低TNF-α (对于单一治疗P <0.01,对于联合治疗P <0.001)。氢氯噻嗪不会引起NOX,cGMP或TNF-α 的显着变化。贝那普利-氨氯地平联合治疗心脏缺血可能是有益的。
  • 15 Clinical pharmacokinetics of amlodipine. 复制标题 收藏 收藏

    【氨氯地平的临床药代动力学。】 复制标题 收藏 收藏
    DOI:10.2165/00003088-199222010-00003 复制DOI
    作者列表:Meredith PA,Elliott HL
    BACKGROUND & AIMS: :Amlodipine is a dihydropyridine calcium antagonist drug with distinctive pharmacokinetic characteristics which appear to be attributable to a high degree of ionisation. Following oral administration, bioavailability is 60 to 65% and plasma concentrations rise gradually to peak 6 to 8h after administration. Amlodipine is extensively metabolised in the liver (but there is no significant presystemic or first-pass metabolism) and is slowly cleared with a terminal elimination half-life of 40 to 50h. Volume of distribution is large (21 L/kg) and there is a high degree of protein binding (98%). There is some evidence that age, severe hepatic impairment and severe renal impairment influence the pharmacokinetic profile leading to higher plasma concentrations and longer half-lives. There is no evidence of pharmacokinetic drug interactions. Amlodipine shows linear dose-related pharmacokinetic characteristics and, at steady-state, there are relatively small fluctuations in plasma concentrations across a dosage interval. Thus, although structurally related to other dihydropyridine derivatives, amlodipine displays significantly different pharmacokinetic characteristics and is suitable for administration in a single daily dose.
    背景与目标: : 氨氯地平是一种二氢吡啶类钙拮抗剂药物,具有独特的药代动力学特征,似乎归因于高度电离。口服给药后,生物利用度为60至65%,血浆浓度在给药后6至8小时逐渐升高至峰值。氨氯地平在肝脏中广泛代谢 (但没有明显的前代谢或首过代谢),并缓慢清除,最终消除半衰期为40至50小时。分布的体积很大 (21 l/kg) 并且存在高度的蛋白质结合 (98%)。有一些证据表明,年龄,严重的肝损害和严重的肾损害会影响药代动力学特征,从而导致更高的血浆浓度和更长的半衰期。没有药代动力学药物相互作用的证据。氨氯地平显示出线性剂量相关的药代动力学特征,并且在稳态下,在整个剂量间隔内血浆浓度的波动相对较小。因此,尽管与其他二氢吡啶衍生物在结构上相关,但氨氯地平显示出明显不同的药代动力学特征,并且适合以每日单一剂量给药。

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