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BMC Pharmacology & Toxicology Jul 2020To investigate the effects of coadministration of esaxerenone with amlodipine on the pharmacokinetics (PK) of each drug, and of esaxerenone on the PK of digoxin. (Clinical Trial)
Clinical Trial
BACKGROUND
To investigate the effects of coadministration of esaxerenone with amlodipine on the pharmacokinetics (PK) of each drug, and of esaxerenone on the PK of digoxin.
METHODS
In three open-label, single-sequence, crossover studies, healthy Japanese males received single oral doses of esaxerenone 2.5 mg (Days 1, 15), with amlodipine 10 mg/day (Days 8-18) (Study 1, N = 24); single doses of amlodipine 2.5 mg (Days 1, 21), with esaxerenone 5 mg/day (Days 8-25) (Study 2; N = 20); or digoxin 0.25 mg/day (Days 1-15) with esaxerenone 5 mg/day (Days 11-15) (Study 3; N = 20). PK parameters and safety were assessed.
RESULTS
Study 1: esaxerenone peak plasma concentration (C) and time to C were unaltered by amlodipine coadministration, but mean half-life was slightly prolonged from 18.5 to 20.9 h. Geometric least-squares mean (GLSM) ratios for C, area under the plasma concentration-time curve (AUC) from zero to last measurable concentration and from zero to infinity for esaxerenone + amlodipine versus esaxerenone were 0.958, 1.154, and 1.173, respectively. Study 2: corresponding GLSM ratios for amlodipine + esaxerenone versus amlodipine were 1.099, 1.185, and 1.214. Study 3: esaxerenone did not markedly alter digoxin PK. GLSM ratios for C, trough plasma concentration, and AUC during a dosing interval for digoxin versus esaxerenone + digoxin were 1.130, 1.088, and 1.072, respectively.
CONCLUSIONS
No drug-drug interactions are expected during combination therapy with esaxerenone and either amlodipine or digoxin, based on a lack of any clinically relevant PK changes.
TRIAL REGISTRATION
Studies 1 and 2: JapicCTI-163379 (registered on 20 September 2016); Study 3: JapicCTI-163443 (registered on 24 November 2016).
Topics: Adult; Amlodipine; Antihypertensive Agents; Asian People; Calcium Channel Blockers; Cross-Over Studies; Digoxin; Drug Interactions; Healthy Volunteers; Humans; Male; Middle Aged; Mineralocorticoid Receptor Antagonists; Pyrroles; Sulfones; Young Adult
PubMed: 32727577
DOI: 10.1186/s40360-020-00423-4 -
High Blood Pressure & Cardiovascular... Nov 2022Hypertension represent the commonest cause of death in 2017. Hypertension is classified into two types which are primary or essential hypertension and secondary... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Hypertension represent the commonest cause of death in 2017. Hypertension is classified into two types which are primary or essential hypertension and secondary hypertension. The perindopril-amlodipine combination showed a significant effect in reduction of the elevated BP and the cardiovascular complications.
AIM
To evaluate the efficacy and safety of a fixed-dose single-pill combination of perindopril-amlodipine in hypertensive patients.
METHODS
We searched PubMed, Medline, SCOPUS, and Web of Science for relevant clinical trials. Quality appraisal was evaluated according to GRADE and we assessed the risk of bias using Cochrane's risk of bias tool. We included the following outcomes: systolic blood pressure, diastolic blood pressure, pulse pressure, mean blood pressure, heart rate, cough, dizziness, headache, and peripheral edema. We performed the analysis of homogeneous data under the fixed-effects model, while analysis of heterogeneous data was analyzed under the random-effects model. We conducted a meta-regression according to the dose.
RESULTS
We included ten clinical trials. The pooled analysis showed that there was a significant reduction of the systolic blood pressure, diastolic blood pressure, pulse plessure, mean blood pressure, and heart rate after the the perindopril-amlodipine combination (MD = 18.96 [14.32, 23.60], P < 0.0001), (MD = 11.90 [8.45, 15.35], P < 0.0001), (MD = 8.44 [6.91, 9.97], P = 0.0001), (MD = 13.07 [5.86, 20.29], P = 0.0004), and (MD = 2.93 [0.89, 4.96], P = 0.005), respectively. The results of the meta-regression revealed that the efficacy is increased by increasing the dose (P < 0.001) CONCLUSION: The use of the perindopril-amlodipine combination had a significant effect on the reduction of SBP, DBP, mean blood pressure, pulse pressure, and HR.
Topics: Humans; Perindopril; Amlodipine; Antihypertensive Agents; Drug Combinations; Hypertension; Blood Pressure; Treatment Outcome
PubMed: 36287359
DOI: 10.1007/s40292-022-00544-3 -
Blood Pressure Monitoring Dec 2023To compare the effects of chlortalidone plus amiloride and amlodipine on blood pressure (BP) variability in patients with hypertension and obstructive sleep apnea... (Randomized Controlled Trial)
Randomized Controlled Trial
Effects of chlorthalidone plus amiloride compared with amlodipine on short-term blood pressure variability in individuals with hypertension and obstructive sleep apnea: a randomized controlled trial.
OBJECTIVE
To compare the effects of chlortalidone plus amiloride and amlodipine on blood pressure (BP) variability in patients with hypertension and obstructive sleep apnea syndrome (OSA).
METHODS
A randomized, controlled, double-blind trial enrolled men and women aged 40 years or older with a diagnosis of OSA (apnea-hypopnea index 10-40 apneas/h of sleep) confirmed by overnight laboratory polysomnography and systolic BP 140-159 mmHg or diastolic BP 90-99 mmHg. Participants were randomized to receive chlortalidone 25 mg plus amiloride 5 mg daily or amlodipine 10 mg daily for 8 weeks. BP variability was calculated from 24-hour ambulatory BP monitoring at baseline and follow-up using the following indices: SD, coefficient of variation, average real variability (ARV), time-rate index, and variability independent of the mean (VIM).
RESULTS
The study included 65 patients, with 33 assigned to the chlortalidone plus amiloride group and 32 to the amlodipine group. Participants in both groups had similar baseline characteristics. Short-term BP variability decreased within groups for SD and ARV indexes for 24-hour systolic BP and daytime systolic BP, but statistically significant time*group interactions were found for sleep systolic SD and VIM, with greater reduction in patients treated with amlodipine.
CONCLUSION
In brief, our study has shown that the use of chlorthalidone in combination with amiloride and amlodipine produces comparable effects on short-term BP variability in patients with hypertension and OSA. Therefore, our findings suggest that BP variability may not be a significant factor when choosing between these medications for the treatment of hypertension and OSA.
Topics: Female; Humans; Male; Amiloride; Amlodipine; Antihypertensive Agents; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Chlorthalidone; Hypertension; Sleep Apnea, Obstructive; Adult; Middle Aged
PubMed: 37466401
DOI: 10.1097/MBP.0000000000000663 -
Minerva Medica Dec 2019The 2018 ESH/ESC guidelines indicate that the first-choice therapy in the majority of hypertensive patients should be a fixed combination of a drug that blocks the... (Review)
Review
The 2018 ESH/ESC guidelines indicate that the first-choice therapy in the majority of hypertensive patients should be a fixed combination of a drug that blocks the renin-angiotensin-aldosterone system and a calcium antagonist or a diuretic. Evidence from the meta-analysis of controlled clinical trials, however, indicates that the classes of drugs that block the renin-angiotensin-aldosterone system should not be considered equivalent as ACE inhibitors have been clearly shown to outperform AT-1 antagonists in preventing myocardial infarction and total mortality. Moreover, studies such as ASCOT and ACCOMPLISH demonstrate a superiority of the ACE-inhibitor/calcium antagonist association over beta-blocker/diuretic associations and especially towards the ACE-inhibitor/diuretic combination, whereas there is no scientific evidence of efficacy with respect to cardiovascular events on the part of AT-1 antagonist/calcium antagonist combinations. Drugs such as ramipril and amlodipine are undoubtedly the reference molecules within their respective classes as numerous controlled clinical studies have demonstrated their effectiveness on cardiovascular events. It is therefore obvious that the availability of a fixed combination with both molecules is a great opportunity for the therapy of the hypertensive patient, considering also the availability of studies that demonstrate its effectiveness on intermediate endpoints associated with high tolerability. So, in accordance with the 2018 ESH/ESC guidelines, the fixed combination ramipril/amlodipine represents a first choice therapy for hypertension.
Topics: Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Calcium Channel Blockers; Drug Combinations; Humans; Hypertension; Practice Guidelines as Topic; Ramipril; Treatment Outcome
PubMed: 31965780
DOI: 10.23736/S0026-4806.19.06282-7 -
The Journal of Clinical Endocrinology... Jul 2021Preoperative blockade with α-blockers is recommended in patients with pheochromocytoma/paraganglioma (PPGL). The data on calcium channel blockade (CCB) in PPGL are... (Randomized Controlled Trial)
Randomized Controlled Trial
CONTEXT
Preoperative blockade with α-blockers is recommended in patients with pheochromocytoma/paraganglioma (PPGL). The data on calcium channel blockade (CCB) in PPGL are scarce.
OBJECTIVE
We aimed to compare the efficacy of CCB and α-blockers on intraoperative hemodynamic instability (HDI) in PPGL.
METHODS
In the interim analysis of this monocentric, pilot, open-label, randomized controlled trial, patients with solitary, secretory, and nonmetastatic PPGL were randomized to oral prazosin gastrointestinal therapeutic system (GITS) (maximum 30 mg, n = 9) or amlodipine (maximum 20 mg, n = 11). The primary outcomes were the episodes and duration of hypertension (systolic blood pressure ≥ 160 mmHg) and hypotension (mean arterial pressure < 60 mmHg) and duration of HDI (hypertension and/or hypotension) as a percentage of total surgical time (from induction of anesthesia to skin closure).
RESULTS
The median (IQR) episodes (2 [1-3] vs 0 [0-1]; P = 0.002) and duration of hypertension (19 [14-42] vs 0 [0-3] minutes; P = 0.001) and intraoperative HDI duration (22.85 ± 18.4% vs 2.44 ± 2.4%; CI, 8.68-32.14%; P 0.002) were significantly higher in the prazosin GITS arm than the amlodipine arm, whereas episodes and duration of hypotension did not differ between the 2 groups. There was no perioperative mortality. One patient had intraoperative ST depression on the electrocardiogram. The drug-related adverse effects were pedal edema (1 in amlodipine), dizziness (1 in prazosin GITS), and tachycardia (6 in prazosin GITS and 3 in amlodipine).
CONCLUSION
Preoperative blockade with amlodipine is an efficacious alternative to prazosin GITS in preventing intraoperative HDI in PPGL. Larger studies that compare preoperative blockade by amlodipine with other α-blockers like phenoxybenzamine and/or doxazosin in PPGL patients are warranted.
Topics: Adolescent; Adrenal Gland Neoplasms; Adult; Aged; Amlodipine; Blood Pressure; Calcium Channel Blockers; Female; Hemodynamics; Humans; Male; Middle Aged; Monitoring, Intraoperative; Pheochromocytoma; Treatment Outcome; Young Adult
PubMed: 33839787
DOI: 10.1210/clinem/dgab231 -
BMC Medicine Jan 2024Current hypertension guidelines recommend combination of an angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker with a calcium-channel blocker or... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Current hypertension guidelines recommend combination of an angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker with a calcium-channel blocker or thiazide diuretic as initial antihypertensive therapy in patients with monotherapy uncontrolled hypertension. However, to what extent these two different combinations are comparable in blood pressure (BP)-lowering efficacy and safety remains under investigation, especially in the Chinese population. We investigated the BP-lowering efficacy and safety of the amlodipine/benazepril and benazepril/hydrochlorothiazide dual therapies in Chinese patients.
METHODS
In a multi-center, randomized, actively controlled, parallel-group trial, we enrolled patients with stage 1 or 2 hypertension from July 2018 to June 2021 in 20 hospitals and community health centers across China. Of the 894 screened patients, 560 eligible patients were randomly assigned to amlodipine/benazepril 5/10 mg (n = 282) or benazepril/hydrochlorothiazide 10/12.5 mg (n = 278), with 213 and 212 patients, respectively, who completed the study and had a valid repeat ambulatory BP recording during follow-up and were included in the efficacy analysis. The primary outcome was the change from baseline to 24 weeks of treatment in 24-h ambulatory systolic BP. Adverse events including symptoms and clinically significant changes in physical examinations and laboratory findings were recorded for safety analysis.
RESULTS
In the efficacy analysis (n = 425), the primary outcome, 24-h ambulatory systolic BP reduction, was - 13.8 ± 1.2 mmHg in the amlodipine/benazepril group and - 12.3 ± 1.2 mmHg in the benazepril/hydrochlorothiazide group, with a between-group difference of - 1.51 (p = 0.36) mmHg. The between-group differences for major secondary outcomes were - 1.47 (p = 0.18) in 24-h diastolic BP, - 2.86 (p = 0.13) and - 2.74 (p = 0.03) in daytime systolic and diastolic BP, and - 0.45 (p = 0.82) and - 0.93 (p = 0.44) in nighttime systolic and diastolic BP. In the safety analysis (n = 560), the incidence rate of dry cough was significantly lower in the amlodipine/benazepril group than in the benazepril/hydrochlorothiazide group (5.3% vs 10.1%, p = 0.04).
CONCLUSIONS
The amlodipine/benazepril and benazepril/hydrochlorothiazide dual therapies were comparable in ambulatory systolic BP lowering. The former combination, compared with the latter, had a greater BP-lowering effect in the daytime and a lower incidence rate of dry cough.
TRIAL REGISTRATION
ClinicalTrials.gov, NCT03682692. Registered on 18 September 2018.
Topics: Humans; Antihypertensive Agents; Amlodipine; Hydrochlorothiazide; Hypertension; Hypotension; China; Cough
PubMed: 38263021
DOI: 10.1186/s12916-023-03244-4 -
Wiadomosci Lekarskie (Warsaw, Poland :... 2022The aim: To analyze the dynamics of daily monitoring of blood pressure, intracardiac (according to echocardiography), peripheral hemodynamics (according to ultrasound of...
OBJECTIVE
The aim: To analyze the dynamics of daily monitoring of blood pressure, intracardiac (according to echocardiography), peripheral hemodynamics (according to ultrasound of the vessels of the lower extremity), the thickness of the intima-media complex (according to carotid sonography) in patients with hypertension the effect of treatment with a combination of lisinopril and amlodipine.
PATIENTS AND METHODS
Materials and methods: The study included 40 patients with hypertension with 2 (29 patients) and 3 (11 patients) degrees of hypertension in combination with AOLE with I-III stages of chronic insufficiency of the lower extremity, which revealed hyperkinetic, eukinetic, and hypokinetic types of hypertension with a predominance of the sympathetic nervous system. The groups are comparable in age, sex, duration of hypertension, and medications received in the previous stages. For antihypertensive therapy, the most common drugs for use were selected - lisinopril + amplodipine in fixed doses of 10 and 5 mg, respectively. If after 2 weeks we did not reduce the mean level of SBP and DBP by 10% or more from baseline, we doubled the dose of lisinopril without changing the dose of amlodipine.
RESULTS
Results: After 6 months of treatment, in particular, an increase in the pulse index - by 24.8%, a decrease in the resistance index - by 21.1%, an increase in linear and volumetric blood velocity - by 25.6% and 27.4%, respectively, while achieving the target blood pressure.
CONCLUSION
Conclusions: It is proved that in the absence of individual contraindications the combination of lisinopril and amlodipine is optimal and universal for effective treatment of patients with hypertension in combination with AOLE in all types of central hemodynamics.
Topics: Humans; Amlodipine; Lisinopril; Antihypertensive Agents; Arteriosclerosis Obliterans; Hypertension; Blood Pressure; Comorbidity; General Practice
PubMed: 36472269
DOI: 10.36740/WLek202210116 -
The Journal of the Association of... Dec 2022Cilnidipine, an upcoming anti-hypertensive drug, is a combined L- and N-type calcium channel blocker. It is proposed to be more efficacious and safer due to its... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Cilnidipine, an upcoming anti-hypertensive drug, is a combined L- and N-type calcium channel blocker. It is proposed to be more efficacious and safer due to its two-pronged approach in treating hypertension.
METHODS
The study was a randomized open-label parallel-group study, conducted in the Department of General Medicine, Sri Ramachandra Medical College Hospital, Chennai, during the period September 2014 to May 2015. 50 patients were randomized to the amlodipine group and 50 to the cilnidipine group. The blood pressure, pulse rate and adverse effects were monitored in each patient over 12 weeks. The difference in the Systolic Blood Pressure(SBP), Diastolic Blood Pressure(DBP) and Heart Rate(HR) before and after treatment within each group, and between the two groups were analyzed using paired and unpaired t tests respectively. The adverse effects reported in each group were analyzed using Chi-square test.
RESULTS
There was no statistically significant difference in the reduction of SBP and DBP between the two groups (p>0.05). The HR however, showed an increase of 1.07/min in the amlodipine group and decreased by 1.16/min in the cilnidipine group. The patients in the cilnidipine group experienced significantly less adverse effects such as pedal edema and palpitations when compared to those in the amlodipine group (p<0.05).
CONCLUSIONS
Cilnidipine therapy is an effective and safe alternative in the treatment of essential hypertension. It can be used as a first line antihypertensive drug since its efficacy is comparable to that of amlodipine with a better safety profile than amlodipine.
Topics: Adult; Amlodipine; Calcium Channel Blockers; Dihydropyridines; Humans; Hypertension; India
PubMed: 35057591
DOI: No ID Found -
Journal of Clinical Laboratory Analysis Dec 2022This study aimed to assess the antioxidant effects of amlodipine in transfusion-dependent β-thalassemia (TDT) patients. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND AND AIM
This study aimed to assess the antioxidant effects of amlodipine in transfusion-dependent β-thalassemia (TDT) patients.
METHODS
This crossover trial consisted of two sequences (AP and PA). In the AP sequence, nine cases received amlodipine 5 mg daily (phase I) and then were switched to placebo (phase II). In PA sequence, 10 patients took the placebo (phase I) and were shifted to amlodipine (phase II). The washout period was 2 weeks. The length of each phase was 6 months. Serum malondialdehyde (MDA, μmol/L), carbonyl (protein CO, μM/L), glutathione (GSH, nM/L), and total antioxidant capacity (TAC, μmol FeSO4/L) were measured in the beginning and at the end of phases I and II. The clinical significance was viewed as a minimum change difference of 5% for each outcome between amlodipine and placebo.
RESULTS
Seventeen cases completed the study. According to the baseline MDA values, the adjusted Hedges's g for MDA was -0.59, 95% confidence interval [CI] -1.26 to 0.08. After controlling the baseline protein CO values, Hedges's g computed for protein CO was -0.11, 95% CI -0.76 to 0.55. The estimated values of the adjusted Hedges's g for GSH and TAC were also 0.26, 95% CI -0.40 to 0.91, and 0.42, 95% CI -0.24 to 1.09, respectively. The change difference for MDA was 8.3% (protein CO 2.2%, GSH 3.1%, and TAC 12.9%).
CONCLUSION
Clinically, amlodipine therapy is an efficacious adjuvant treatment with conventional iron chelators for improving the levels of MDA and TAC in patients with TDT.
Topics: Humans; Amlodipine; Antioxidants; beta-Thalassemia; Cross-Over Studies; Glutathione; Malondialdehyde; Oxidative Stress; Double-Blind Method
PubMed: 36357338
DOI: 10.1002/jcla.24752 -
Journal of Medical Toxicology :... Jan 2020Toxicity related to calcium-channel blockers remains a significant cause of morbidity and mortality. Amlodipine-induced shock is unique in that its mechanism of action...
INTRODUCTION
Toxicity related to calcium-channel blockers remains a significant cause of morbidity and mortality. Amlodipine-induced shock is unique in that its mechanism of action is thought to occur in part via the release of nitric oxide (NO) in the peripheral vasculature. Specific therapeutic interventions, including methylene blue (an NO scavenger), have been suggested, but efficacy studies are severely limited. To facilitate a larger porcine study into the effect of various interventions on amlodipine toxicity, we undertook this model development and feasibility study.
METHODS
Intravenous amlodipine was prepared by dissolving commercially obtained amlodipine tablets in dimethylsulfoxide. The concentration of the drug was verified using ultraviolet spectroscopy. We administered this solution to three animals in order to determine a toxic dose, capable of facilitating a two-arm study of amlodipine toxicity.
RESULTS
The first pig died rapidly after the bolus infusion. The second pig developed mild toxicity, but the dissolution of the plastic tubing by the solvent and subsequent leakage limited the interpretability of the result. The third animal developed expected toxicity with an infusion rate between 2.0 and 5.5 mg/kg/h.
CONCLUSION
This study demonstrates a potentially repeatable model of amlodipine-induced toxic shock using intravenous administration of amlodipine and several methodological considerations for researchers undertaking similar work.
Topics: Amlodipine; Animals; Calcium Channel Blockers; Cardiotoxicity; Disease Models, Animal; Feasibility Studies; Hemodynamics; Shock, Cardiogenic; Sus scrofa
PubMed: 31385194
DOI: 10.1007/s13181-019-00721-2