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

Hong, Soon Jun; Ahn, Tae Noon; Baek, Sang Hong; Cho, Wook Hyun; Jeon, Hyee Kyoung; Kyun, Jun; Yoon, Myeong‐Ho; Lee, Kwan Jeh; Lim, Do Sun

doi:10.1016/j.clinthera.2006.04.008

Cited by 12 publications

(9 citation statements)

References 36 publications

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“…Amlodipine (Pfizer Inc., New York, NY, USA) is a well-established, long-acting CCB for the treatment of hypertension, including patients with diabetes 20–22. Studies in hypertensive patients have highlighted the additional benefit of titrating amlodipine from 5 mg to 10 mg once daily with regard to lowering BP,23–27 including Asian patients 26. However, because the efficacy of increasing amlodipine dose from 5 mg to 10 mg has thus far only been evaluated in a small number of patients with hypertension and diabetes, we conducted this post-hoc analysis of 710 patients with known diabetic status from six clinical trials, which included 100 diabetic patients.…”

Section: Introductionmentioning

confidence: 99%

Uptitrating amlodipine significantly reduces blood pressure in diabetic patients with hypertension: a retrospective, pooled analysis

Jeffers

Bhambri

Robbins

2014

VHRM

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Diabetic patients with hypertension are approximately twice as likely to develop cardiovascular disease as non-diabetic patients with hypertension. Given that hypertension affects ∼60% of patients with diabetes, effective blood pressure (BP) management is important in this high-risk population. This post-hoc analysis pooled data from six clinical studies to quantify additional BP efficacy achieved when titrating hypertensive diabetic patients from amlodipine 5 mg to 10 mg. Approximately half of the diabetic patients were male (44/98; 44.9%) with a mean (standard deviation [SD]) age of 60.6 (9.6) years and a baseline mean (standard error [SE]) systolic blood pressure/diastolic blood pressure (SBP/DBP) of 150.8 (1.30)/87.5 (0.94) mmHg while on amlodipine 5 mg (159.1 [1.40]/92.6 [0.94] mmHg prior to treatment). In comparison, 350/610 (57.4%) non-diabetic patients were male with a mean (SD) age of 58.7 (11.1) years and baseline mean (SE) SBP/DBP of 150.3 (0.62)/90.9 (0.41) mmHg while on amlodipine 5 mg (160.0 [0.67]/96.2 [0.45] mmHg prior to treatment). Increasing amlodipine from 5 mg to 10 mg lowered sitting SBP by −12.5 mmHg (95% confidence interval (CI): −15.5, −9.5; P<0.0001) and DBP by −6.0 mmHg (−7.4, −4.6; P<0.0001) in diabetic patients; and SBP by −12.4 mmHg (−13.5, −11.3; P<0.0001) and DBP by −7.3 mmHg (−8.0, −6.7; P<0.0001) in non-diabetic patients. In total, 12.0% (95% CI: 6.4, 20.0) of diabetic patients achieved their BP goal versus 46.4% (42.4, 50.4) of non-diabetic patients after titration to amlodipine 10 mg. Overall, 22.0% of diabetic patients experienced 31 adverse events (AEs) and 28.9% of non-diabetic patients experienced 282 AEs. Serious AEs were reported by one (1.0%) diabetic and five (0.8%) non-diabetic patients. In this analysis, increasing amlodipine from 5 mg to 10 mg produced a clinically significant reduction in the BP of diabetic hypertensive patients, similar to non-diabetic patients, highlighting the importance of optimizing amlodipine titration in this high-risk population.

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Section: Introductionmentioning

confidence: 99%

Uptitrating amlodipine significantly reduces blood pressure in diabetic patients with hypertension: a retrospective, pooled analysis

Jeffers

Bhambri

Robbins

2014

VHRM

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“…1) isac alciumchannel blockerdeveloped fororaladministration thathasbeen widelyu sed in therapys incethe early 1980s [1][2][3].Amlodipine wasdeveloped byPfizerand is marketed primarilyasab esylatesalt(amlodipine besylate,C AS 111470-99-6). Inrecenty ears others alts of amlodipine havebeen developed,suchasamlodipine maleate( CAS 88150-47-4) [4];amlodipine camsylate (CAS 652969-01-2) [5];and amlodipine orotate( CAS 914941-70-1) [6].Amlodipine maleatecould obtain a considerable reduction of side effect [7], and hasbeen widelyu sed in clinicalp racticee vers ince.…”

Section: Introductionmentioning

confidence: 99%

Liquid Chromatography–Mass Spectrometry Method for the Determination of Amlodipine in Human Plasma and its Application in a Bioequivalence Study

Zou¹,

Yu²,

Ge³

et al. 2011

Arzneimittelforschung

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A sensitive and selective liquid chromatographic-mass spectrometric (LC-MS) method for the determination of amlodipine (CAS 88150-42-9) in human plasma has been developed. Sample preparation was based on liquid-liquid extraction using NaOH and cyclohexane. Analytical determination was carried out on a C18 column interfaced with a single quadrupole mass spectrometer. Positive electrospray ionization was employed as the ionization source. The mobile phase was 10 mmol/L ammonium acetate solution-methanol (30:70, v/v) at the flow rate of 0.2 mL/min. The method was linear in the concentration range of 0.2-20 ng/mL. The lower limit of quantification was 0.2 ng/mL. Amlodipine was sensitive to UV light. The method was validated in terms of accuracy, precision, absolute recovery, and stability. The intra- and interday relative standard deviation across three validation runs over the entire concentration range was less than 8.17%. The accuracy determined at three concentrations (0.4, 2.0 and 10 ng/mL for amlodipine maleate) was within +/- 3.17% in terms of relative error. The method herein described was successfully applied for the evaluation of pharmacokinetic profiles of amlodipine maleate tablets in 20 healthy volunteers. The results showed that AUC, Tmax, Cmax and T 1/2 between the test and reference formulation have no significant difference (P > 0.05). The relative bioavailability was 103.7 +/- 12.3%.

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“…These salts include camsylate, nicotinate, adipate, and orotate, 15 , 16 and have been shown not to be different from the besylate salt form in terms of efficacy and tolerability in patients with mild to moderate hypertension. 17 – 20 In particular, amlodipine orotate shows enhanced absorption after oral administration in vagotomized dogs, which mimic the low gastric acidity (hypoacidity or anacidity) condition in patients. 21 Thus, although dogs might be different from humans, amlodipine orotate is likely preferable for patients with low gastric acidity.…”

Section: Discussionmentioning

confidence: 99%

Bioequivalence evaluation of two amlodipine salts, besylate and orotate, each in a fixed-dose combination with olmesartan in healthy subjects

Lee¹,

Kim²,

Jung³

et al. 2015

DDDT

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A fixed-dose combination of amlodipine and olmesartan is used to treat high blood pressure in patients whose hypertension is not sufficiently controlled with either drug alone. The objective of this study was to evaluate the bioequivalence of two fixed-dose combinations, ie, amlodipine orotate/olmesartan medoxomil 10/40 mg and amlodipine besylate/olmesartan medoxomil 10/40 mg, in healthy subjects. A randomized, open-label, single-dose, two-sequence, two-period, crossover study was conducted in 30 healthy adult volunteers. Blood samples were collected for up to 72 hours post-dose in each period. Safety data included the results of physical examinations, clinical laboratory tests, vital signs, an electrocardiogram, and adverse events. For both amlodipine and olmesartan, the 90% confidence intervals for the geometric mean ratios of AUClast and time to peak plasma concentration fell within the bioequivalence acceptance criteria. The two fixed-dose combinations showed similar safety profiles. Amlodipine orotate/olmesartan medoxomil 10/40 mg was bioequivalent to amlodipine besylate/olmesartan medoxomil 10/40 mg.

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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

Cited by 12 publications

References 36 publications

Uptitrating amlodipine significantly reduces blood pressure in diabetic patients with hypertension: a retrospective, pooled analysis

Uptitrating amlodipine significantly reduces blood pressure in diabetic patients with hypertension: a retrospective, pooled analysis

Liquid Chromatography–Mass Spectrometry Method for the Determination of Amlodipine in Human Plasma and its Application in a Bioequivalence Study

Bioequivalence evaluation of two amlodipine salts, besylate and orotate, each in a fixed-dose combination with olmesartan in healthy subjects

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