Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study compared the efficacy and safety of 8 weeks of open treatment with the dihydropyridine calcium antagonists amlodipine and nitrendipine in mild-to-moderate hypertension. Interim analysis of data from 74 patients (43 male, 31 female) showed that amlodipine normalized diastolic blood pressure (less than or equal to 90 mmHg) in 95% of patients compared with 83% of nitrendipine-treated patients. Nitrendipine produced a statistically significant increase in heart rate at 2 and 4 weeks of therapy but there was no significant change in heart rate in amlodipine-treated patients. Amlodipine-treated patients reported fewer adverse events (26%) than did the nitrendipine-treated group (47%), with two patients from the nitrendipine group discontinuing treatment due to treatment-related adverse events. Adverse events in the amlodipine-treated group were mild to moderate. The incidence of flushing was higher in nitrendipine-treated patients (25%) than in amlodipine-treated patients (10%). This relative difference in the incidence of vasodilator-related side effects is probably explained by the gradual onset of effect with amlodipine.
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PMID:Amlodipine compared to nitrendipine for the treatment of mild-to-moderate hypertension. 183 37

Amlodipine is a long acting dihydropyridine calcium antagonist recently introduced for the treatment of angina and hypertension. In order to document its stability in vitro and to develop a pharmacokinetic model in rabbits, a new reversed-phase liquid chromatography (LC) assay with UV detection was developed. The method utilized a C18 column (250 x 4.6 mm i.d.) with a mobile phase composed of a mixture of methanol 0.04 M ammonium acetate-acetonitrile (38:38:24, v/v/v) containing 0.02% triethylamine (final pH 7.1). Under these conditions, the retention times of amlodipine and the internal standard desipramine were 10.6 and 12.9 min, respectively. Using 1 ml of plasma, sensitivity of the assay was 2.5 ng ml-1 at which the RSD was 11%. The standard curve was linear from 2.5 to 100 ng ml-1 (r2 = 0.990), and the mean RSD at this concentration range was 6.8%. The pharmacokinetic model was developed in rabbits which provides results similar to those in dogs, but at less expense. The assay was also applied to a stability study comparing amlodipine and nifedipine in pH 3 and pH 7 ammonium acetate buffers and in methanol. Amlodipine was considerably more stable than nifedipine under all conditions. Finally the assay was applied to a pharmacokinetic study in rabbits (n = 6) after a single 1 mg kg-1 intravenous dose. The mean half-life (t1/2) of amlodipine was 6.5 h, the systemic clearance (CL) was 4.8 l h-1 kg-1 and the apparent volume of distribution at steady state (Vdss) was 30.2 l kg-1.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Liquid chromatography assay for amlodipine: chemical stability and pharmacokinetics in rabbits. 184 Jan 30

Pharmacodynamics and disposition of amlodipine, a dihydropyridine calcium antagonist, were compared between elderly and young patients with hypertension. Elderly (mean +/- SD; age, 68 +/- 3 years) and young (35 +/- 5 years) patients received single intravenous amlodipine doses followed by oral administration once daily for a total of 12 weeks. After intravenous administration, elderly patients had prolonged elimination half-life values (58 +/- 11 versus 42 +/- 8 hours; p less than 0.01) caused by decreased clearance (19 +/- 5 versus 25 +/- 7 L/hr; p less than 0.01). After a 3-months oral treatment washout period, half-life tended to be prolonged in the elderly patients (69 +/- 20 hours for the elderly patients versus 53 +/- 14 hours for the young patients; difference not significant) and was not markedly different from the short-term intravenous measurement. Both systolic and diastolic blood pressure were significantly decreased from baseline throughout the treatment period, with greater decreases in elderly patients for both systolic and diastolic pressure. When amlodipine plasma concentration was correlated to change in mean blood pressure after short-term intravenous doses, elderly patients had a greater decrease than young patients at a given drug concentration. However, after long-term oral administration, elderly and young patients had comparable decreases in mean blood pressure at a given drug concentration, and the increased antihypertensive effect in the elderly was associated with somewhat higher amlodipine plasma concentration. Amlodipine administered once daily is an effective antihypertensive agent in elderly patients and young patients with essential hypertension.
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PMID:Effects of amlodipine, a long-acting dihydropyridine calcium antagonist in aging hypertension: pharmacodynamics in relation to disposition. 214 47

Although calcium antagonists were originally developed for use in the management of patients with angina pectoris, they are now used in the management of other cardiovascular disorders, including hypertension. More recently, the calcium antagonists have been under investigation for their potential protective role in atherosclerosis. Coupled with these new possibilities for therapeutic use are the development of new, long-acting, tissue-specific calcium antagonists. Amlodipine belongs to this group, and although it is a dihydropyridine-based calcium antagonist, its pharmacologic profile differs from that of other dihydropyridine-based calcium antagonists. Differences include: different pH optimum for receptor binding, different rates of association and dissociation, and differences in allosteric interaction with the diltiazem and verapamil binding sites. Amlodipine, when given orally to rabbits receiving a high-cholesterol diet, reduces atheroma formation. Evidence of its ability to protect the vasculature is provided by its ability to significantly increase (p less than 0.001) survival in stroke-prone hypertensive rats.
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PMID:Protecting the vasculature: an eye toward the future. 214 59

Amlodipine, a new long-acting dihydropyridine calcium antagonist, was compared with placebo and atenolol in 125 patients with mild to moderate systemic hypertension [supine diastolic blood pressure (DBP) 90-114 mm Hg]. Patients received placebo for 4 weeks, followed by a random allocation to an 8-week double-blind, once-daily treatment with amlodipine (n = 41), atenolol (n = 43), or placebo (n = 41). The changes in 24-h post-dose blood pressure (BP) from baseline to final visit for amlodipine (mean daily dose 8.8 mg, range 5-10 mg) were -12.8 +/- 2.0/ -10.1 +/- 1.2 mm Hg in supine BP and -11.5 +/- 2.3/-9.8 +/- 1.1 mm Hg in standing BP (p less than 0.001); for atenolol (mean daily dose 83.7 mg, range 50-100 mg), the changes from baseline were -11.3 +/- 2.3/-11.7 +/- 1.3 mm Hg in supine BP and -13.3 +/- 3.1/-12.3 +/- 1.5 mm Hg in standing BP (p less than 0.001); for placebo, the changes from baseline were -0.9 +/- 2.8/-3.5 +/- 0.9 mm Hg in supine BP and -1.6 +/- -2.6/-4.0 +/- 1.0 mm Hg in standing BP. In the study, goal response was defined as a supine DBP of less than 90 mm Hg or its decrease by greater than or equal to 10 mm Hg. The response rates were similar for atenolol (65%) and amlodipine (61%). Both active therapies were significantly more effective than placebo. Heart rate was significantly lowered by atenolol only.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A randomized placebo-controlled comparison of amlodipine and atenolol in mild to moderate systemic hypertension. 246 16

Calcium antagonists are a biochemically heterogeneous group of drugs that share the property of blocking the entry of calcium into cells by voltage-operated channels in cardiac and smooth muscle. They are useful in the management of angina pectoris and hypertension. The drugs available at present include nifedipine, verapamil, and diltiazem. All three drugs have similar pharmacokinetic properties of low and variable bioavailability, high first-pass metabolism, short elimination half-life, and active metabolites. The pharmacokinetics of calcium antagonists are relevant, because in individual patients the intensity and duration of the pharmacological effect is related to the level of drug in plasma. Amlodipine is a new dihydropyridine calcium antagonist in advanced clinical development. It has a completely different pharmacokinetic profile. It is water soluble and photostable, and has a long half-life of 35-50 h. Amlodipine is slowly absorbed, its absolute bioavailability is high, and it is extensively metabolized in the liver. The long half-life is associated with a prolonged (greater than 24 h) duration of pharmacodynamic action. Amlodipine, because of its novel pharmacokinetics, may offer practical advantages over existing calcium antagonists in the long-term treatment of cardiovascular disease.
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PMID:Pharmacokinetics of calcium antagonists. 246 22

The database on amlodipine, a calcium antagonist of the 1,4-dihydropyridine class, was obtained from clinical trials in the United States, Canada, and Europe. The clinical dossier describing the efficacy and safety of once-daily amlodipine in the treatment of hypertension is extensive, well organized, and logically designed. It shows that amlodipine is an effective antihypertensive drug, providing smooth 24-h blood pressure control without orthostatic hypotension, and that it is well tolerated as monotherapy and in combination with other antihypertensive drugs. A total of 18 clinical studies were reviewed; 1,091 patients received amlodipine whereas 805 received either placebo or another drug for comparison. The common entry criteria include a supine and standing diastolic blood pressure in the range 95-114 mg Hg. Blood pressure measurements were made 24 h after the last dose of amlodipine in all studies. Amlodipine is clearly superior to placebo and induces a clinically significant reduction in blood pressure (mean reductions 23/13 mm Hg supine, 24/12 upright in one representative study) with similar heart rates in the supine and standing positions. Blood pressure control shows a smooth profile over 24 h with once-daily dosing, and there is no tolerance with long-term administration of the drug. The useful clinical dose is in the range of 5-10 mg, which is well tolerated in comparison with clinical doses of atenolol, hydrochlorothiazide, or verapamil. Amlodipine can be used as monotherapy in a large proportion of patients but may also be combined with a beta-blocker, diuretic, or angiotensin converting enzyme inhibitor. Based on these observations, amlodipine may prove to be an attractive addition to our antihypertensive armamentarium.
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PMID:Amlodipine in hypertension: an overview of the clinical dossier. 246 23

Amlodipine is a long-acting dihydropyridine-based calcium antagonist developed for use on a once-a-day basis. Experiments were undertaken to establish whether the chronic administration of amlodipine prevents the rise in blood pressure in spontaneously hypertensive rats (SHR), and whether it attenuates cardiac hypertrophy caused by hypertension. The experiments were performed in spontaneously hypertensive rats, and normotensive Wistar-Kyoto (WKY) and Sprague-Dawley (SD) rats. Amlodipine was given orally to provide a daily intake of 10 mg kg-1 day-1. The rats were 8 weeks old at the start of the therapy. In the SHR, but not in the WKY or SD rats, the blood pressure was reduced (p less than 0.01) after 30 weeks in the rats receiving amlodipine but not in the placebo-treated rats. At the same time the heart-to-body-weight ratio was reduced in the amlodipine-treated SHR but not in the SD or WKY rats. This same amlodipine regimen (10 mg kg-1 day-1 orally) or amlodipine i.v. (0.25 mg/kg, 5 h before excising the hearts) improved functional recovery (p less than 0.01) of hearts "stunned" by 10 min ischemia and attenuated (p less than 0.05) calcium ion gain on reperfusion after 30 to 60 min ischemia. These results indicate that prophylactic therapy with amlodipine lowers blood pressure in hypertensive rats, prevents hypertension-induced hypertrophy, and exerts a cardiac-protective effect during short periods of ischemia.
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PMID:The effect of amlodipine on hypertension-induced cardiac hypertrophy and reperfusion-induced calcium overload. 246 27

The antihypertensive efficacy of once-daily amlodipine was studied in a group of 30 patients with mild to moderate hypertension in a double-blind, placebo-controlled, parallel-group study. The dose range of amlodipine was 2.5-10.0 mg daily adjusted every 2 weeks for a total treatment period of 8 weeks. Amlodipine produced a significant reduction in blood pressure compared with placebo, the mean difference between baseline and 8 weeks (corrected for placebo effect) being 16/12 mm Hg supine, 14/4 mm Hg standing. Blood pressure returned to baseline values during a terminal 4-week washout period with placebo. There were no significant effects on heart rate. Two patients experienced slight ankle edema while receiving amlodipine 10.0 mg daily but the active drug was otherwise well tolerated.
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PMID:Once-daily amlodipine in the treatment of mild to moderate hypertension. 246 34

A multicenter, placebo-controlled trial assessed the antihypertensive efficacy and safety of different doses of amlodipine in patients with mild to moderate hypertension. Amlodipine was administered once daily in doses of 1.25-2.5 mg (low-dose group), 2.5-5.0 mg (medium-dose group), and 5.0-10.0 mg (high-dose group) during 8 weeks; doses were titrated within each group after 4 weeks of double-blind treatment if normotension or "target" blood pressures had not been achieved. After 4 weeks, supine systolic and diastolic blood pressures were significantly reduced in the medium and high-dose groups compared with placebo; standing blood pressures were significantly reduced only in the high-dose group. After 8 weeks of treatment, all blood pressures were significantly reduced except standing systolic and diastolic blood pressures in the low-dose group. There was a low incidence of side effects, which were generally mild to moderate in intensity, and there were no clinically significant effects on pulse rate, electrocardiogram, or body weight. Amlodipine produces a dose-related reduction in blood pressures with once-daily dosing, 2.5 mg being the minimum effective dose, and is well tolerated.
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PMID:Amlodipine: a double-blind evaluation of the dose-response relationship in mild to moderate hypertension. 246 35


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