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At least 19 recordsLinked to original sources

PubMed2006

Comparison of efficacy and tolerability of amlodipine orotate versus amlodipine besylate in adult patients with mild to moderate hypertension: a multicenter, randomized, double-blind, placebo-controlled, parallel-group, 8-week follow-up, noninferiority trial.

OBJECTIVE: The purpose of this study was to compare the efficacy and tolerability of amlodipine orotate with those of amlodipine besylate in Korean patients with mild to moderate hypertension. METHODS: This multicenter, randomized, double-blind, placebo-controlled, parallel-group study was designed as a noninferiority study. To be included in the study, previously untreated patients had to have a sitting diastolic blood pressure (SiDBP) of 90 to 109 mm Hg. Previously treated patients had to discontinue their current annhypertensive medications and have a baseline SiDBP between 90 and 109 mm Hg after a 2-week washout period. Patients who met the inclusion criteria were randomly assigned to receive 5 mg amlodipine orotate or 5 mg amlodipine besylate for 8 weeks. The medication dose was doubled (10 mg QD for either amlodipine orotate or amlodipine besylate) 4 weeks after enrollment if SiDBP was >or=90 mm Hg. The primary efficacy analysis was noninferiority of the difference in mean trough SiDBP changes from baseline for amlodipin eorotate as compared with amlodipine besylate after 8 weeks of treatment. For the secondary efficacy analysis, 2 other measures were analyzed after 8 weeks of treatment. The SiDBP response rate was defined as an SiDBP measurement<90 mm Hg at the last clinical follow-up visit or an absolute reduction of >or=10 mm Hg in SiDBP from baseline until the last clinical follow-up visit. In addition, noninferiority of the difference in mean trough sitting systolic blood pressure (SiSBP) changes from baseline was analyzed for amlodipine orotate as compared with amlodipine besylate. The drug compliance rate was estimated by pillcount. RESULTS: Eligible patients (n=109; 43 women and 66 men) were randomly assigned to receive amlodipine orotate (n=53) or amlodipine besylate (n=56). No significant differences were found in sex, age, weight, or current smoking between the groups (all, P=NS). The proportion of patients with previous antihypertensive medications was not different between the groups (47.2% [25/53] in the amlodipine orotate group and 50.0% [28/56] in the amlodipine besylate group; P=NS). No significant differences were found in baseline SiDBP (mean [SD], 100 [6] mm Hg [range, 90-109 mm Hg] in the amlodipine orotate group and 100 [6] mm Hg [range, 90-108 mm Hg] in the amlodipine besylate group; P=NS) or in baseline SiSBP (mean [SD], 149 [14] mm Hg [range, 125-179 mm Hg] in the amlodipine orotate group and 146 [10] mm Hg [range, 123-167 mm Hg] in the amlodipine besylate group; p=NS). The mean (SD) changes in SiDBP were -15.6 (6.3) mm Hg for the amlodipine orotate group and -14.5 (5.5) mm Hg for the amlodipine besylate groups was 1.1 (5.9) mm Hg (95% CI, -0.87 to infinity), and because the lower boundary of the 95% CI was greater than -5 mm Hg, amlodipine orotate was considered noninferior to amlodipine besylate. The response rate was 48 of 51 (94.1%) in the amlodipine orotate group compared with 50 (92.6%) of 54 in the amlodipine besylate group after 8 weeks of treatment (P=NS). The mean (SD) compliance rates were 97.6% (3.6%) in the amlodipine orotate group and 96.5% (4.3%) in the amlodipine besylate group (P=NS). The incidence of drug-related adverse events (AEs) was similar between the groups (1/53 [1.9%]) in the amlodipine orotate group vs 4/55 [7.3%] in the amlodipine besylate group; P=NS). The most common drug-related AE overall was peripheral edema (2/55 [3.6%]), and the most common of all the AEs was upper respiratory tract infection (4/55 [7.3%]) in the amlodipine besylate group. The most common drug-related AE was headache (1/53 [1.9%]) in the amlodipine orotate group and peripheral edema (2/55 [3.6%]) in the amlodipine besylate group. No severe AEs were found in either group. CONCLUSION: The reduction in SiDBP after 8 weeks of amlodipine orotate treatment was noninferior to that of amlodipine besylate in these Korean patients with mild to moderate hypertension. The SiDBP response rate and the reduction in SISBP after 8 weeks of amlodipine orotate treatment were not significantly different from those of amlodipine besylate treatment. Both agents were wel tolerated.

Adult↗

PubMed2004

Multicentric, clinical trial of S-Amlodipine 2.5 mg versus Amlodipine 5 mg in the treatment of mild to moderate hypertension--a randomized, double-blind clinical trial.

OBJECTIVE: To compare the efficacy and tolerability of 2.5 mg of S-Amlodipine with 5 mg of Amlodipine in the treatment of mild to moderate hypertension in a double blind, double dummy, randomized, comparative clinical trial. METHOD AND MATERIALS: Two hundred OPD patients (97 women and 103 men) with mean age 53.4 +/- 5.58 years, with stage I and stage 2 hypertension were enrolled for the study after obtaining informed written consent. Twelve patients were dropped out as lost to follow up. Ninety seven patients in the S-Amlodipine 2.5 mg treatment group and ninety one patients in the Amlodipine 5 mg treatment group completed the study. Those with a history of angina pectoris, myocardial infarction or recent cerebrovascular accident in the past six months and those with stage 3 and stage 4 hypertension were excluded from the study. Those showing a history of secondary hypertension were also excluded from the study. For the first two weeks all patients received dummy tablets of both S-Amlodipine and Amlodipine, as a wash out therapy and to get the actual blood pressure reading. After two weeks, enrolled patients received a preparation containing either S-Amlodipine (containing 2.5 mg of S-Amlodipine) and dummy tablets of Amlodipine or Amlodipine besylate (containing 5 mg of racemic Amlodipine) and dummy tablets of S-Amlodipine once daily for a period of six weeks. RESULTS: The results were analyzed by Student's 't' test The reduction in the average systolic and diastolic blood pressure, in the standing, supine and sitting postures in the S-Amlodipine group as well as in the Amlodipine group after six weeks of treatment was highly significant (P < or = 0.0001). The baseline values for average systolic blood pressure in standing, supine and sitting positions in the S-Amlodipine 2.5 mg treatment group were found to be 164.12 +/- 10.28, 165.72 +/- 10.88 and 165.24 +/- 10.66 mm of Hg respectively, which after treatment of six weeks changed to 144.9 +/- 7.4, 146.04 +/- 8.56 and 145.36 +/- 8.32 mm of Hg. The baseline values for average systolic blood pressure in standing, supine and sitting positions in the Amlodipine 5 mg treatment group were found to be 164.57 +/- 10.36, 166.47 +/- 10.58 and 165.81 +/- 10.54 mm of Hg respectively, which after treatment of six weeks changed to 154.42 +/- 6.33, 147.23 +/- 7.11 and 146.57 +/- 7.54 mm of Hg. The baseline values for average diastolic blood pressure in standing, supine and sitting positions in the S-Amlodipine 2.5 mg treatment group were found to be 99.63 +/- 6.22, 101.13 +/- 7.18 and 100.59 +/- 6.6 mm of Hg respectively, which after treatment of six weeks changed to 86.0 +/- 4.70, 87.18 +/- 5.20 and 86.27 +/- 5.68 mm of Hg. While the baseline values for average diastolic blood pressure in standing, supine and sitting positions in the Amlodipine 5 mg treatment group were found to be 98.95 +/- 5.54, 100.86 +/- 6.71 and 100.38 +/- 6.38 mm of Hg respectively, which after treatment of six weeks changed to 86.19 +/- 4.77, 87.52 +/- 5.44 and 87.33 +/- 5.98 mm of Hg. However the difference in the average reduction in systolic and diastolic blood pressures, in the two treatment groups, in the sitting, supine and the standing positions was not found to be statistically significant (p > 0.1) (CI = 0.95). There was no statistically significant change in the levels of serum creatinine, SGOT, SGPT, HDL, LDL, triglyceride and total cholesterol in patients receiving Amlodipine 5 mg. The reduction in total cholesterol as well as triglyceride level in the S-Amlodipine 2.5 mg treatment group was found to be greater but it failed to show any statistically significant difference. CONCLUSION: S-Amlodipine 2.5 mg is found to be equivalent in its efficacy and tolerability when compared to Amlodipine 5 mg in the treatment of mild to moderate hypertension.

Amlodipine↗

PubMed2005

Results of a multicenter, 8-week, parallel-group, randomized,double-blind, double-dummy, Phase III clinical trial to evaluate the efficacy and tolerability of amlodipine maleate versus amlodipine besylate in Korean patients with mild to moderate hypertension.

BACKGROUND: Recently, amlodipine maleate was developed and tested in preclinical and Phase I clinical trials in Korea. The studies found pharmacokinetics and pharmacodynamics similar to those of amlodipine besylate. OBJECTIVE: The aim of this study was to compare the efficacy and tolerability of amlodipine maleate with those of amlodipine besylate in Korean patients with mild to moderate hypertension. METHODS: This was a multicenter, 8-week, parallel-group, randomized, double-blind, double-dummy, Phase III clinical trial. Eligible patients were Korean, aged 18 to 75 years, had hypertension, and were either taking antihypertensive medications or had a documented sitting diastolic blood pressure of 90 to 109 mm Hg. After a washout period of 2 weeks, patients were randomized to amlodipine maleate or amlodipine besylate for 8 weeks. In both groups, the medications were initiated at 5 mg QD. At day 29, the medication dose was increased to 10 mg QD if sitting diastolic blood pressure (SiDBP) was > or = 90 mm Hg. RESULTS: One hundred eighteen patients were enrolled. Fifty-seven patients received amlodipine maleate (29 men, 28 women; mean [SD] age, 49.0 [11.4] years) and 61 received amlodipine besylate (35 men, 26 women; mean [SD] age, 51.6 [9.4] years). Baseline mean (SD) values for sitting systolic blood pressure and SiDBP were 152.0 (12.2) mm Hg and 98.1 (5.6) mm Hg, respectively, for the amlodipine maleate group and 153.4 (14.0) mm Hg and 98.1 (5.5) mm Hg, respectively, for the amlodipine besylate group. In this population, amlodipine maleate was not inferior to amlodipine besylate: the lower limit of the 2-sided 95% CI for the treatment difference in SiDBP was greater than -4 mm Hg. The between-group difference in SiDBP response rate (the proportion of patients who experienced adequate SiDBP reductions) did not reach statistical significance: 85.7% (42/49) for the amlodipine maleate group and 91.8% (45/49) for the amlodipine besylate group. Compliance rates were similar between groups, with mean (SD) compliance rates of 97.4% (2.8%) and 97.1% (3.6%) in the amlodipine maleate and amlodipine besylate groups, respectively. Also, there were no significant differences in the incidences of drug-related clinical and laboratory adverse events; the most common were headache, flushing, facial edema, and paresthesia. CONCLUSION: In this population, the efficacy and tolerability observed with amlodipine maleate were similar to those seen with amlodipine besylate.

Adult↗

PubMed2000

Influence of baseline values on lipids, lipoproteins and fibrinolytic parameters during amlodipine treatment of hypertension in Japanese patients.

Twenty-four Japanese hypertensive patients of both sexes, grouped as having 'medium' and 'high' baseline total lipid values, had their serum lipids, lipoproteins and plasma fibrinolytic parameters, renin and noradrenaline levels determined after 3 months of amlodipine treatment. For the patients with 'medium baseline values', total plasminogen activator inhibitor-1 (PAI-1) and t-PA-PAI-1 complex levels decreased, while the changes in lipids and lipoproteins were not significant after amlodipine treatment. For the patients with 'high baseline values', the mean triglyceride and very low density lipoprotein cholesterol (VLDLC) levels were reduced while the reductions in total and free PAI-1 and the increase in tissue plasminogen (t-PA) levels were not significant after amlodipine treatment. Negative correlations were observed between t-PA and high density lipoprotein cholesterol (HDLC) and HDLC/total cholesterol (TC) ratio in the patients with 'medium baseline values' while t-PA positively correlated with HDLC/TC ratio in patients with 'high baseline values'. The mean levels of renin and noradrenaline remained unchanged before and after amlodipine treatment in the two baseline groups. These findings show that baseline lipid levels of the hypertensive patients could influence lipids and fibrinolytic parameters differently during amlodipine treatment. The baseline lipid levels also influenced the metabolic association between lipids and fibrinolytic function in hypertensive patients during amlodipine treatment. The baseline total lipid values could therefore provide explanations for the complex metabolic interaction between lipids and fibrinolytic function as well as for the antiatherogenic actions of amlodipine treatment in hypertensive patients.

Aged↗

PubMed2001

Once-daily treatment of patients with hypertension: a placebo-controlled study of amlodipine and benazepril vs amlodipine or benazepril alone.

OBJECTIVE: To compare the efficacy, tolerability, and safety of once-daily therapy with amlodipine 5 mg/benazepril 10 mg vs amlodipine 5 mg, benazepril 10 mg, and placebo. DESIGN: Randomised, double-blind, placebo-controlled, parallel-group, multicentre trial. SETTING: Twenty-two clinical centres, including private practice groups and academic research clinics. PATIENTS: A total of 530 patients between 21 and 80 years of age with essential hypertension were screened for the study, and 454 were randomised to treatment with amlodipine 5 mg/benazepril 10 mg, amlodipine 5 mg, benazepril 10 mg, or placebo for 8 weeks. RESULTS: Amlodipine 5 mg/benazepril 10 mg produced greater reductions from baseline in sitting diastolic blood pressure than amlodipine 5 mg (P < 0.03), benazepril 10 mg (P < 0.001), and placebo (P < 0.001). The response rate in the amlodipine 5-mg/benazepril 10-mg treatment group (66.4%) was better than that observed in the amlodipine 5-mg (50.0% P < 0.02), benazepril 10-mg (38.3% P < 0.001), and placebo (24.4% P < 0.001) groups. There was no significant difference in heart rate among the four groups. The incidence of oedema in the amlodipine 5-mg/benazepril 10-mg (1.7%) group was somewhat less than that in the amlodipine 5-mg (4.5%) group. CONCLUSIONS: Therapy with amlodipine 5 mg/benazepril 10 mg was well tolerated and was superior to amlodipine 5 mg, benazepril 10 mg, and placebo in reducing sitting diastolic blood pressure in patients with essential hypertension.

Adult↗

PubMed2006

Comparative pharmacokinetic and pharmacodynamic characteristics of amlodipine besylate and amlodipine nicotinate in healthy subjects.

BACKGROUND AND AIM: Amlodipine, a dihydropyridine calcium antagonist, is prescribed for the management of angina and hypertension, and is sold as amlodipine besylate. However, a new salt formulation, amlodipine nicotinate, has recently been developed. Here, we evaluated the comparative pharmacokinetic and pharmacodynamic characteristics of the nicotinate and besylate forms of amlodipine. SUBJECTS AND METHODS: A randomized, 2-way crossover study was conducted in 18 healthy male volunteers to compare the pharmacokinetics and pharmacodynamics of these two forms, i.e. amlodipine nicotinate (test) and amlodipine besylate (reference), after administration of a single dose of 5 mg of each drug and a washout period between doses of 4 weeks. Blood samples for the pharmacokinetic analysis of amlodipine were obtained over the 144-hour period after administration. Systolic and diastolic blood pressures and pulse rates were recorded immediately prior to each blood sampling. RESULTS: All participants completed both treatment periods, and no serious adverse events occurred during the study period. After administering a single dose of each formulation, mean AUC0-infinity and Cmax values were 190.91+/-60.49 ng x h/ml and 3.87+/-1.04 ng/ml for the test formulation and 203.15+/-52.05 ng x h/ml and 4.01+/-0.60 ng/ml for the reference formulation, respectively. The 90% confidence intervals of test/reference mean ratios for AUC0- infinity and Cmax fell within the predetermined equivalence range of 80 - 125%. Pharmacodynamic profiles including systolic and diastolic blood pressures and pulse rates exhibited no significant differences between the two formulations. CONCLUSION: The two amlodipine formulations showed similar pharmacokinetic and pharmacodynamic characteristics and the new amlodipine formulation, amlodipine nicotinate, was found to be equivalent for pharmacokinetics to the currently available amlodipine besylate with respect to the rate and extent of amlodipine absorption.

Administration, Oral↗

PubMed1999

Comparison of controlled-onset, extended-release verapamil with amlodipine and amlodipine plus atenolol on exercise performance and ambulatory ischemia in patients with chronic stable angina pectoris.

This multicenter, randomized, double-blind, parallel group, placebo lead-in, placebo-controlled study compared the antianginal and anti-ischemic effects of once-daily bedtime dosing of controlled-onset extended-release (COER-24) verapamil to a once-daily morning dosing of amlodipine +/- atenolol in patients with chronic stable angina. A total of 551 patients with exercise-induced myocardial ischemia and evidence of coronary artery disease were randomized to a 4-week, forced-dose titration treatment period with (1) COER-24 verapamil 240 mg titrated to 480 mg at bedtime (n = 173), (2) amlodipine 5 mg titrated to 10 mg/day (n = 149), (3) amlodipine 5 mg (titrated to 10 mg) plus atenolol 50 mg/day in the A.M. (n = 154), or (4) placebo (n = 75). Treadmill exercise tolerance testing (standard Bruce protocol), and 48-hour ambulatory electrocardiographic (Holter) monitoring were performed at the end of placebo lead-in and double-blind treatment. Each active treatment significantly improved symptom-limited exercise duration and time to moderate angina (p < or = 0.01 vs placebo). For patients with baseline ischemia, amlodipine resulted in a statistically significant increase in total duration of ischemic episodes compared with placebo, whereas COER-24 verapamil and amlodipine plus atenolol resulted in statistically significant decreases compared with placebo and amlodipine. Heart rate at onset of ischemic episodes and ST product were also significantly increased with amlodipine (p < 0.05) compared with either COER-24 or amlodipine plus atenolol. COER-24 and amlodipine alone or in combination with atenolol improved exercise capacity in patients with angina pectoris. COER-24 verapamil monotherapy or amlodipine plus atenolol combination therapy were more effective than amlodipine monotherapy in decreasing ambulatory myocardial ischemia, especially during the hours of 6 A.M. to 12 noon.

Adrenergic beta-Antagonists↗

PubMed2006

A novel stealth liposomal topotecan with amlodipine: apoptotic effect is associated with deletion of intracellular Ca2+ by amlodipine thus leading to an enhanced antitumor activity in leukemia.

The objectives of the present study were to define whether amlodipine induces apoptosis and what mechanism is involved in the process in human resistant and non-resistant leukemia cells following co-administration of stealth liposomal topotecan with amlodipine, a novel antiresistant liposomes developed by our institution. In three leukemias, K562, HL-60, and multidrug resistant (MDR) HL-60, cytotoxicity of topotecan was potentiated by amlodipine, while topotecan alone was resistant to MDR HL-60 cells. In two selected K562 or MDR HL-60 cells, the apoptotic effects were increased by addition of amlodipine, showing a dose-dependent manner. The activities of caspase 3 and 7 (marked as caspase 3/7), and caspase 8 were significantly activated by topotecan with amlodipine co-treated as the stealth liposomes. The deletions of intracellular Ca2+ stores induced by amlodipine correlated with the activated activities of caspase 3/7, or 8, respectively. In xenograft model with MDR HL-60 in nude mice, antitumor activity of stealth liposomal topotecan with amlodipine was significantly enhanced as compared to that of stealth liposomal topotecan or topotecan alone. In conclusion, apoptotic effect is associated with deletion of intracellular Ca2+ by amlodipine through activation of caspase 8 and then 3/7 activities. The enhanced antitumor activities by stealth liposomal topotecan with amlodipine are mainly due to the potentiating apoptotic effect and reversing the resistance by amlodipine. Stealth liposomal encapsulation of anticancer agent with a modulator may provide a novel strategy for improving the chemotherapeutic effects.

Amlodipine↗

PubMedDate not supplied

Treatment of patients with essential hypertension: amlodipine 5 mg/benazepril 20 mg compared with amlodipine 5 mg, benazepril 20 mg, and placebo.

This multicenter, double-masked, randomized, parallel-group study compared the efficacy, tolerability, and safety of amlodipine 5 mg/benazepril 20 mg, amlodipine 5 mg, benazepril 20 mg, and placebo in patients with essential hypertension. After a placebo run-in period, 308 patients (all white) were randomized to treatment groups and took medication once daily for 8 weeks. Blood pressure was measured after 4 and 8 weeks of treatment in the 23- to 26-hour period after dosing. Patients wore a noninvasive blood pressure monitor for 24 hours before randomization and before the final visit. Investigators recorded adverse experiences at randomization and at study weeks 4 and 8, and obtained specimens for laboratory testing at randomization and at study week 8. Three hundred seven patients were evaluated for efficacy, and 308 for tolerability and safety. At end point (the last postrandomization measurement for each patient), the reduction in mean sitting diastolic blood pressure with the amlodipine 5 mg/benazepril 20 mg treatment was statistically significantly greater than with any comparative therapy. The results of 24-hour monitoring showed that the amlodipine/benazepril treatment, unlike monotherapy, maintained the hourly mean diastolic blood pressure at < or = 90 mm Hg. A responder rate of 87.0% was observed with amlodipine 5 mg/benazepril 20 mg versus 67.5%, 53.3%, and 15.8% with amlodipine, benazepril, and placebo, respectively. This difference between the amlodipine/benazepril treatment group and each comparative single-agent treatment group was statistically significant. Drug-related adverse events occurred in 15.6% of patients in the amlodipine/benazepril group and in 24.7%, 6.5%, and 11.7% of patients in the amlodipine, benazepril, and placebo groups, respectively. Edema occurred less often in the amlodipine/benazepril group than in the amlodipine group. Overall, once-daily therapy with amlodipine 5 mg/benazepril 20 mg provided an antihypertensive effect that was statistically and clinically superior to amlodipine 5 mg alone, benazepril 20 mg alone, and placebo, was well tolerated, and was associated with less edema than the amlodipine treatment.

Administration, Oral↗

PubMed1996

Effect of amlodipine on morbidity and mortality in severe chronic heart failure. Prospective Randomized Amlodipine Survival Evaluation Study Group.

BACKGROUND: Previous studies have shown that calcium-channel blockers increase morbidity and mortality in patients with chronic heart failure. We studied the effect of a new calcium-channel blocker, amlodipine, in patients with severe chronic heart failure. METHODS: We randomly assigned 1153 patients with severe chronic heart failure and ejection fractions of less than 30 percent to double-blind treatment with either placebo (582 patients) or amlodipine (571 patients) for 6 to 33 months, while their usual therapy was continued. The randomization was stratified on the basis of whether patients had ischemic or nonischemic causes of heart failure. The primary end point of the study was death from any cause and hospitalization for major cardiovascular events. RESULTS: Primary end points were reached in 42 percent of the placebo group and 39 percent of the amlodipine group, representing a 9 percent reduction in the combined risk of fatal and nonfatal events with amlodipine (95 percent confidence interval, 24 percent reduction to 10 percent increase; P=0.31). A total of 38 percent of the patients in the placebo group died, as compared with 33 percent of those in the amlodipine group, representing a 16 percent reduction in the risk of death with amlodipine (95 percent confidence interval, 31 percent reduction to 2 percent increase; P=0.07). Among patients with ischemic heart disease, there was no difference between the amlodipine and placebo groups in the occurrence of either end point. In contrast, among patients with nonischemic cardiomyopathy, amlodipine reduced the combined risk of fatal and nonfatal events by 31 percent (P=0.04) and decreased the risk of death by 46 percent (P<0.001). CONCLUSIONS: Amlodipine did not increase cardiovascular morbidity or mortality in patients with severe heart failure. The possibility that amlodipine prolongs survival in patients with nonischemic dilated cardiomyopathy requires further study.

Aged↗

PubMed2000

Pharmacokinetics of repeated oral doses of amlodipine and amlodipine plus telmisartan in healthy volunteers.

This open-label, crossover study was performed to establish if there is evidence for interaction between telmisartan, an angiotensin II antagonist, and amlodipine, a class II (dihydropyridine) calcium channel antagonist, on the basis of pharmacokinetics and safety. In a two-way crossover trial, 12 healthy Caucasian males were randomized to receive once daily for 9 days oral amlodipine 10 mg with or without oral telmisartan 120 mg. After a washout period of > or = 13 days, the subjects were switched to the other medication regimen. The geometric means of the primary pharmacokinetic parameters at steady state (day 9) for amlodipine when given alone were the following: maximum plasma concentration (Cmax) 17.7 ng/mL, area under the plasma concentration-time curve (AUC) 331 ng.h/mL, and renal clearance 39.5 mL/min, with 8% of the total amlodipine dose being excreted. When concomitant telmisartan was given, the respective values were 18.7 ng/mL, 352 ng.h/mL, and 43.0 mL/min, with 9.4% of the total amlodipine dose being excreted renally. The limits of the 90% confidence intervals (CIs) for the ratios of these steady-state parameters were 0.97 to 1.14 for Cmax and 0.98 to 1.16 for AUC; both were within the predefined reference range (0.8 to 1.25) for bioequivalence. The high intersubject variability in urinary amlodipine excretion resulted in bioequivalence not being demonstrated for renal clearance. Adverse effects were few, mild to moderate in intensity, and transient whether amlodipine was given alone or with telmisartan. Vital signs, except for blood pressure, and clinical laboratory values were unaffected by either medication. The findings of this study show that concomitant telmisartan and amlodipine may be administered as there is no clinically significant variation in primary pharmacokinetic parameters of amlodipine in the presence of telmisartan, and the safety of the combination is comparable to that of amlodipine alone.

Administration, Oral↗

PubMed1993

Randomized placebo-controlled trial of amlodipine in vasospastic angina. Amlodipine Study 160 Group.

OBJECTIVES: This study was designed to assess the efficacy and safety of amlodipine, a long-acting calcium channel blocker, in patients with vasospastic angina. BACKGROUND: Previous studies have established the value of short-acting calcium channel blockers in the treatment of coronary spasm. METHODS: Fifty-two patients with well documented vasospastic angina were entered into the present study. After a single-blind placebo run-in period, patients were randomized (in a double-blind protocol) to receive either amlodipine (10 mg) or placebo every morning for 4 weeks. Twenty-four patients received amlodipine and 28 received placebo. All patients were given diaries in which to record both the frequency, severity, duration and circumstances of anginal episodes and their intake of sublingual nitroglycerin tablets. RESULTS: The rate of anginal episodes decreased significantly (p = 0.009) with amlodipine treatment compared with placebo and the intake of nitroglycerin tablets showed a similar trend. Peripheral edema was the only adverse event seen more frequently in amlodipine-treated patients. No patient was withdrawn from the double-blind phase of the study because of an adverse event. Patients who completed the double-blind phase as responders to amlodipine or as nonresponders to placebo were offered the option of receiving amlodipine in a long-term, open label extension phase. During the extension, the daily dose of amlodipine was adjusted to 5 or 15 mg if needed and the rate of both anginal episodes and nitroglycerin tablet consumption showed statistically significant decreases between baseline and final assessment. CONCLUSION: This study suggests that amlodipine given once daily is efficacious and safe in the treatment of vasospastic angina.

Adult↗

PubMed1999

Evaluation of amlodipine dosing for conversion of nifedipine extended-release to amlodipine in the treatment of hypertension.

OBJECTIVE: To evaluate the appropriate dosing of amlodipine when converting patients from nifedipine extended-release (nifedipine ER) to amlodipine in the treatment of hypertension. METHODS: Patients of the Outpatient Clinic of Cheyenne Veterans Affairs Medical Center, Wyoming, receiving nifedipine ER for the management of hypertension (systolic BP or SBP > 140 mm Hg and diastolic BP or DBP > 90 mm Hg), participated in this study. Nifedipine ER was changed to amlodipine on entry into this study. An inclusion criterion was the BP had to be under control (SBP < 140 mm Hg and DBP < 90 mm Hg) before the switch. The BP in each study patient was monitored once weekly (once every 2 wk in some patients) for a total of six clinic visits or until BP was under control. Dosing titration of amlodipine was required in 16 of 27 patients after the switch. To assess the adequacy of the conversion, the statistical significance of the difference of the mean BP values before and at the end of the monitoring period was estimated by using the t-test for paired data. RESULTS: Twenty-seven male patients completed this study. BP in all study patients was adequately controlled after nifedipine ER was switched to amlodipine. The SBP and DBP values before and after the switch were similar (SBP: 124 +/- 12 vs. 126 +/- 9 mm Hg, CI of the mean difference -6.10 to 1.80; DBP: 76 +/- 8 vs. 76 +/- 7 mm Hg, CI of the mean difference -2.45 to 3.63). Initial amlodipine dose of 5 or 10 mg once daily was used in our study. No serious adverse effects were observed in any of the study patients after the drug switch. CONCLUSIONS: This study indicates the amlodipine dosage of 5 or 10 mg once daily can be used when nifedipine ER is converted to amlodipine in the treatment of hypertension. Dosage titration of amlodipine may be required to obtain adequate control of BP.

Adult↗

PubMed2001

Comparative effects of candesartan cilexetil and amlodipine in patients with mild systemic hypertension. Comparison of Candesartan and Amlodipine for Safety, Tolerability and Efficacy (CASTLE) Study Investigators.

The comparative antihypertensive efficacy and tolerability of the angiotensin II receptor blocker candesartan cilexetil and the calcium channel blocker amlodipine were evaluated in an 8-week, multicenter, double-blind, randomized, parallel-group, forced-titration study in 251 adult patients (45% women, 16% black) with mild hypertension (stage 1). Following a 4- to 5-week placebo run-in period, patients with sitting diastolic blood pressure (BP) of 90 to 99 mm Hg received candesartan cilexetil 16 mg (n = 123) or amlodipine 5 mg (n = 128) once daily. After 4 weeks of double-blind treatment, patients were uptitrated to candesartan cilexetil 32 mg or amlodipine 10 mg once daily. There were no significant differences between the candesartan cilexetil and amlodipine regimens for reducing BP; mean systolic BP/diastolic BP reductions were -15.2/-10.2 mm Hg versus -15.4/-11.3 mm Hg, respectively (p = 0.88/0.25). Overall, 79% of patients on candesartan cilexetil and 87% of those on amlodipine were controlled (diastolic BP <90 mm Hg). A total of 3.3% of patients on candesartan cilexetil discontinued treatment, compared with 9.4% of patients on amlodipine, including 2.4% versus 4.7% for adverse events and 0% versus 1.6% for peripheral edema, respectively. Peripheral edema, the prespecified primary tolerability end point, occurred with significantly greater frequency in patients on amlodipine (22.1%; mild 8.7%, moderate 11.8%, severe 1.6%) versus patients on candesartan cilexetil (8.9%; mild 8.1%, moderate 0.8%) (p = 0.005). Candesartan cilexetil and amlodipine are both highly effective in controlling BP in patients with mild hypertension. Candesartan cilexetil offers a significant tolerability advantage with respect to less risk of developing peripheral edema.

Amlodipine↗

PubMed1997

Role of cytokines in the mechanism of action of amlodipine: the PRAISE Heart Failure Trial. Prospective Randomized Amlodipine Survival Evaluation.

OBJECTIVES: We sought to determine whether the beneficial effects of amlodipine in heart failure may be mediated by a reduction in tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) levels. We postulated that TNF-alpha and IL-6 levels may also have predictive value in patients with congestive heart failure (CHF). BACKGROUND: The molecular mechanism for progression of CHF may involve cytokine overexpression. The effect of amlodipine on cytokine levels in patients with CHF is unknown. METHODS: In the Prospective Randomized Amlodipine Survival Evaluation (PRAISE) trial, we used enzyme-linked immunosorbent assay to measure plasma levels of TNF-alpha in 92 patients and IL-6 in 62 patients in New York Heart Association functional classes III and IV randomized to receive amlodipine (10 mg/day) or placebo. Blood samples were obtained for cytokine measurement at baseline and at 8 and 26 weeks after enrollment. RESULTS: The baseline amlodipine and placebo groups did not differ in demographics and cytokine levels. Mean (+/- SD) plasma levels of TNF-alpha were 5.69 +/- 0.32 pg/ml, and those of IL-6 were 9.23 +/- 1.26 pg/ml at baseline. These levels were elevated 6 and 10 times, respectively, compared with those of normal subjects (p < 0.001). Levels of TNF-alpha did not change significantly over the 26-week period (p = 0.69). However, IL-6 levels were significantly lower at 26 weeks in patients treated with amlodipine versus placebo (p = 0.007 by the Wilcoxon signed-rank test). An adverse event-CHF or death-occurred more commonly in patients with higher IL-6 levels. CONCLUSIONS: Amlodipine lowers plasma IL-6 levels in patients with CHF. The beneficial effect of amlodipine in CHF may be due to a reduction of cytokines such as IL-6.

Aged↗

PubMed2000

Restenosis and clinical outcome in patients treated with amlodipine after angioplasty: results from the Coronary AngioPlasty Amlodipine REStenosis Study (CAPARES).

OBJECTIVES: Our intent was to investigate the effect of the dihydropyridine calcium channel blocker amlodipine on restenosis and clinical outcome in patients undergoing percutaneous transluminal coronary angioplasty (PTCA). BACKGROUND: Amlodipine has sustained vasodilatory effects and relieves coronary spasm, which may reduce luminal loss and clinical complications after PTCA. METHODS: In a prospective, double-blind design, 635 patients were randomized to 10 mg of amlodipine or placebo. Pretreatment with the study drug started two weeks before PTCA and continued until four months after PTCA. The primary angiographic end point was loss in minimal lumen diameter (MLD) from post-PTCA to follow-up, as assessed by quantitative coronary angiography (QCA). Clinical end points were death, myocardial infarction, coronary artery bypass graft surgery and repeat PTCA (major adverse clinical events). RESULTS: Angioplasty was performed in 585 patients (92.1%); 91 patients (15.6%) had coronary stents implanted. Follow-up angiography suitable for QCA analysis was done in 236 patients in the amlodipine group and 215 patients in the placebo group (per-protocol group). The mean loss in MLD was 0.30 +/- 0.45 mm in the amlodipine group versus 0.29 +/- 0.49 mm in the placebo group (p = 0.84). The need for repeat PTCA was significantly lower in the amlodipine versus the placebo group (10 [3.1%] vs. 23 patients [7.3%], p = 0.02, relative risk ratio [RR]: 0.45, 95% confidence interval [CI]: 0.22 to 0.91), and the composite incidence of clinical events (30 [9.4%] vs. 46 patients (14.5%), p = 0.049, RR: 0.65, CI: 0.43 to 0.99) within the four months follow-up period (intention-to-treat analysis). CONCLUSIONS: Amlodipine therapy starting two weeks before PTCA did not reduce luminal loss, but the incidence of repeat PTCA and the composite major adverse clinical events were significantly reduced during the four-month follow-up period after PTCA with amlodipine as compared with placebo.

Amlodipine↗

PubMed1998

A comparative study of once-daily amlodipine versus twice-daily diltiazem controlled release (CR) in the treatment of stable angina pectoris. Amlodipine Study Group.

A multicenter, double-blind study was performed to compare the efficacy and safety of the calcium antagonists, amlodipine and diltiazem controlled release (CR), in patients with stable angina pectoris. One hundred and thirty-two patients were randomized to receive either amlodipine (5-10 mg) once daily or diltiazem CR (90-120 mg) twice daily for 8 weeks. A standard bicycle exercise tolerance test was used for the primary efficacy assessment. The median time to 1 mm ST-segment depression and time to onset of chest pain were increased by 16% (P < 0.0001) and 13% (P < 0.0001) with amlodipine, and by 16% (P < 0.0001) and 7% (P = 0.009) with diltiazem CR, respectively. Amlodipine, but not diltiazem CR, also produced a significant improvement in the median time to end of exercise of 5% (P < 0.0002), although the between-treatment difference for this parameter was not statistically significant. The number of angina attacks and nitroglycerin (NTG) tablet consumption were similar with both agents. Amlodipine was withdrawn in 3% and diltiazem CR in 9% of patients due to adverse events. The adverse events were reported by 15% of patients on amlodipine and 26% of those on diltiazem CR. The results from this study demonstrate that both drugs have a comparable therapeutic effect and possibly that amlodipine was better tolerated in patients with stable angina. Furthermore, amlodipine has the advantage of once-daily dosing and so may also be beneficial in ensuring good patient compliance.

Adult↗

PubMed1989

A comparison of amlodipine, verapamil and placebo in the treatment of mild to moderate hypertension. Amlodipine Study Group.

This is a double blind parallel group comparison in patients with mild-moderate hypertension, of amlodipine, verapamil and placebo. One hundred and sixty patients entered the double blind phase. In the amlodipine group the mean supine and standing systolic pressures at week 12 were respectively lowered from baseline by 11.9 mmHg and 11.3 mmHg more than for the placebo group (P = 0.0001). Diastolic blood pressures were also significantly reduced. With verapamil the mean supine and standing systolic blood pressure at week 12 were reduced by 7.7 mmHg and 8.3 mmHg more on verapamil than on placebo (P = 0.0083). Blood pressures of the amlodipine group were lower 24 hour post-dose than verapamil 12 hours post dose. The responder rates after eight weeks of double blind therapy were amlodipine 72.3%, verapamil 47.8% and placebo 32.6%. Body weight after verapamil increased by mean 0.9 kg, after amlodipine by 0.2 kg and after placebo decreased by 0.2 kg. Six patients were withdrawn because of adverse effects (3 amlodipine, 2 verapamil, 1 placebo). The number of patients with adverse effects possibly related to therapy were 22/53 for amlodipine, 19/54 for verapamil and 14/53 for placebo. Both drugs were, overall, well tolerated, effective and had no unexpected adverse effects.

Adult↗