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Saudi Pharmaceutical Journal : SPJ :... Sep 2023The objective of this study was to investigate the effects of cinnamon on the pharmacodynamic (PD) & pharmacokinetic (PK) of amlodipine in hypertensive rats. The...
The objective of this study was to investigate the effects of cinnamon on the pharmacodynamic (PD) & pharmacokinetic (PK) of amlodipine in hypertensive rats. The hypertensive control group of Wistar rats received L-NAME (40 mg/kg, daily, orally) only. The cinnamon group of rats was treated with cinnamon (200 mg/kg, daily, orally) along with L-NAME. Following 14 days treatment period, blood pressures of rats were monitored at designated intervals over 24 h utilizing a tail-cuff system for measuring blood pressure. To assess the oral PK; amlodipine was administered as a single oral dose of 1 mg/kg to rats and blood samples were collected at specified intervals over 24 h and analysed by UPLC-LC MS/MS. Synergistic decreased in rat's blood pressure was observed in presence of cinnamon + amlodipine. Simultaneous administration of cinnamon ameliorates the C and AUC of amlodipine, the C and AUC was 11.04 ± 1.01 ng/ml and 113.76 ± 5.62 ng h/ml for the cinnamon + amlodipine group as compared to 4.12 ± 0.49 ng/ml and 48.59 ± 4.28 ng h/ml for the amlodipine alone group. The study demonstrates that the use of cinnamon considerably decreases the blood pressure levels and enhances the PK parameters of amlodipine in hypertensive rats.
PubMed: 37638214
DOI: 10.1016/j.jsps.2023.101737 -
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 -
Journal of Clinical Hypertension... Oct 2020Hypertension and dyslipidemia are important risk factors for cardiovascular disease. However, the clinical outcomes of fixed-dose combination (FDC) versus...
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.
Topics: Amlodipine; Antihypertensive Agents; Atorvastatin; Drug Combinations; Drug Therapy, Combination; Dyslipidemias; Humans; Hypertension; Mortality; Taiwan; Treatment Outcome
PubMed: 32862551
DOI: 10.1111/jch.14016 -
Genes Aug 2022Objective: This study describes the single nucleotide polymorphisms (SNPs) in amlodipine-associated genes and assesses their correlation with blood pressure control...
Objective: This study describes the single nucleotide polymorphisms (SNPs) in amlodipine-associated genes and assesses their correlation with blood pressure control among South African adults with hypertension. Methods: In total, 304 hypertensive patients on amlodipine treatment belonging to the indigenous Swati, Xhosa and Zulu population groups of South Africa were recruited between June 2017 and June 2019. Participants were categorized into: controlled (blood pressure < 140/90 mmHg) and uncontrolled (blood pressure ≥ 140/90 mmHg) hypertension. Thirteen SNPs in amlodipine pharmacogenes with a high PharmGKB evidence base were selected and genotyped using MassArray (Agena BioscienceTM). Logistic regression was fitted to identify significant associations between the SNPs and blood pressure control with amlodipine. Results: The majority of the participants were females (76.6%), older than 45 years (89.1%) and had uncontrolled hypertension (52.3%). Of the 13 SNPs genotyped, five SNPs, rs1042713 (minor allele frequency = 45.9%), rs10494366 (minor allele frequency = 35.3%), rs2239050 (minor allele frequency = 28.7%), rs2246709 (minor allele frequency = 51.6%) and rs4291 (minor allele frequency = 34.4%), were detected among the Xhosa participants, while none were detected among the Swati and Zulu tribal groups. Variants rs1042713 and rs10494366 demonstrated an expression frequency of 97.5% and 79.5%, respectively. Variant TA genotype of rs4291 was significantly associated with uncontrolled hypertension. No association was established between blood pressure response to amlodipine and the remaining four SNPs. Conclusions: This study reports the discovery of five SNPs in amlodipine genes (rs2239050, rs2246709, rs4291, rs1042713 and rs10494366) among the indigenous Xhosa-speaking tribe of South Africa. In addition, the TA genotype of rs4291 was associated with blood pressure control in this cohort. These findings might open doors for more pharmacogenomic studies, which could inform innovations to personalised anti-hypertensive treatment in the ethnically diverse population of South Africa.
Topics: Adult; Amlodipine; Blood Pressure; Female; Humans; Hypertension; Male; Polymorphism, Single Nucleotide; South Africa
PubMed: 36011305
DOI: 10.3390/genes13081394 -
Drug Design, Development and Therapy 2022The combined administration of tadalafil, a phosphodiesterase-5 inhibitor, and amlodipine, a calcium channel blocker, can be a promising therapeutic option for... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
The combined administration of tadalafil, a phosphodiesterase-5 inhibitor, and amlodipine, a calcium channel blocker, can be a promising therapeutic option for hypertension patients with erectile dysfunction. This study aimed to examine the pharmacokinetic drug interaction between tadalafil and amlodipine and the tolerability of their combined administration in healthy male subjects.
SUBJECTS AND METHODS
Healthy volunteers (N = 24) were randomly assigned to one of the six sequences that consisted of three treatments: tadalafil (5 mg) alone, amlodipine (10 mg) alone, and tadalafil plus amlodipine. The study drugs were administered orally for 9 d, and the collected serial blood samples were analyzed up to 72 h after the last dosing. Pharmacokinetic parameters were calculated using non-compartmental analysis.
RESULTS
For tadalafil, geometric mean ratios (GMRs) (90% confidence interval (CI)) of the combined therapy over the monotherapy were 1.57 (1.46-1.68) for AUC and 1.34 (1.24-1.45) for C. For amlodipine, the GMRs (90% CI) of AUC and C were 0.93 (0.90-0.97) and 0.95 (0.91-0.99), respectively. The severity of all observed adverse events (AEs) related to the study drugs was mild, and the frequency of AEs of the combined administration was not significantly different from the monotherapy.
CONCLUSION
A substantial pharmacokinetic drug interaction between tadalafil and amlodipine was observed with respect to the concentration of tadalafil when administered concomitantly. However, the dose range of the combined administration of tadalafil and amlodipine in the present study was well tolerated by the subjects.
Topics: Administration, Oral; Amlodipine; Area Under Curve; Cross-Over Studies; Drug Interactions; Healthy Volunteers; Humans; Male; Tadalafil
PubMed: 35221673
DOI: 10.2147/DDDT.S348897 -
World Journal of Nephrology May 2022Chronic kidney disease (CKD) and hypertension (HTN) are closely associated with an overlapping and intermingled cause and effect relationship. Decline in renal functions... (Review)
Review
Chronic kidney disease (CKD) and hypertension (HTN) are closely associated with an overlapping and intermingled cause and effect relationship. Decline in renal functions are usually associated with a rise in blood pressure (BP), and prolonged elevations in BP hasten the progression of kidney function decline. Regulation of HTN by normalizing the BP in an individual, thereby slowing the progression of kidney disease and reducing the risk of cardiovascular disease, can be effectively achieved by the anti-hypertensive use of calcium channel blockers (CCBs). Use of dihydropyridine CCBs such as amlodipine (ALM) in patients with CKD is an attractive option not only for controlling BP but also for safely improving patient outcomes. Vast clinical experiences with its use as monotherapy and/or in combination with other anti-hypertensives in varied conditions have demonstrated its superior qualities in effectively managing HTN in patients with CKD with minimal adverse effects. In comparison to other counterparts, ALM displays robust reduction in risk of cardiovascular endpoints, particularly stroke, and in patients with renal impairment. ALM with its longer half-life displays effective BP control over 24-h, thereby reducing the progression of end-stage-renal disease. In conclusion, compared to other classes of CCBs, ALM is an attractive choice for effectively managing HTN in CKD patients and improving the overall quality of life.
PubMed: 35733653
DOI: 10.5527/wjn.v11.i3.86 -
Cells Mar 2021(1) Background: Recently, influences of antihypertensive treatment on the renin-angiotensin-aldosterone system (RAAS) has gained attention, regarding a possible...
(1) Background: Recently, influences of antihypertensive treatment on the renin-angiotensin-aldosterone system (RAAS) has gained attention, regarding a possible influence on inflammatory and anti-inflammatory pathways. We aimed to study the effects of newly initiated antihypertensive drugs on angiotensin (Ang) II and Ang (1-7) as representers of two counter-regulatory axes. (2) Methods: In this randomized, open-label trial investigating RAAS peptides after the initiation of perindopril, olmesartan, amlodipine, or hydrochlorothiazide, Ang II and Ang (1-7) equilibrium concentrations were measured at 8 a.m. and 12 a.m. at baseline and after four weeks of treatment. Eighty patients were randomized (1:1:1:1 fashion). (3) Results: Between the four substances, we found significant differences regarding the concentrations of Ang II ( < 0.0005 for 8 a.m., 12 a.m.) and Ang (1-7) ( = 0.019 for 8 a.m., <0.0005 for 12 a.m.) four weeks after treatment start. Ang II was decreased by perindopril ( = 0.002), and increased by olmesartan ( < 0.0005), amlodipine ( = 0.012), and hydrochlorothiazide ( = 0.001). Ang (1-7) was increased by perindopril and olmesartan ( = 0.008/0.002), but not measurably altered by amlodipine and hydrochlorothiazide ( = 0.317/ 0.109). (4) Conclusion: The initiation of all first line antihypertensive treatments causes early and distinct alterations of equilibrium angiotensin levels. Given the additional AT1R blocking action of olmesartan, RAAS peptides shift upon initiation of perindopril and olmesartan appear to work in favor of the anti-inflammatory axis compared to amlodipine and hydrochlorothiazide.
Topics: Antihypertensive Agents; Female; Humans; Hypertension; Male; Middle Aged; Renin-Angiotensin System
PubMed: 33802464
DOI: 10.3390/cells10030534 -
Journal of Clinical Hypertension... May 2023We compared the efficacy and safety of third-standard-dose triple and third-standard-dose dual antihypertensive combination therapies in patients with mild to moderate... (Randomized Controlled Trial)
Randomized Controlled Trial
We compared the efficacy and safety of third-standard-dose triple and third-standard-dose dual antihypertensive combination therapies in patients with mild to moderate hypertension. This was a phase II multicenter, randomized, double-blind, parallel-group trial. After a 4-week placebo run-in period, 245 participants were randomized to the third-dose triple combination (ALC group; amlodipine 1.67 mg + losartan potassium 16.67 mg + chlorthalidone 4.17 mg) or third-dose dual combination (AL group; amlodipine 1.67 mg + losartan potassium 16.67 mg, LC group; losartan potassium 16.67 mg + chlorthalidone 4.17 mg, AC group; amlodipine 1.67 mg + chlorthalidone 4.17 mg) therapy groups and followed up for 8 weeks. The mean systolic blood pressure (BP) reduction was -18.3 ± 13.2, -13.0 ± 13.3, -16.3 ± 12.4, and -13.8 ± 13.2 mmHg in the ALC, AL, LC, and AC groups, respectively. The ALC group showed significant systolic BP reduction compared to the AL and AC groups at weeks 4 (P = .010 and P = .018, respectively) and 8 (P = .017 and P = .036, respectively). At week 4, the proportion of systolic BP responders was significantly higher in the ALC group (42.6%) than in the AL (22.0%), LC (23.3%), and AC (27.1%) groups (P = .013, P = .021, and P = .045, respectively). At week 8, the proportion of systolic and diastolic BP responders was significantly higher in the ALC group (59.7%) than in the AL (39.3%) and AC (42.4%) groups (P = .022 and P = .049, respectively) at week 8. Third-standard-dose triple antihypertensive combination therapy demonstrated early effective BP control compared to third-standard-dose dual combination therapies, without increasing adverse drug reactions in patients with mild-to-moderate hypertension.
Topics: Humans; Antihypertensive Agents; Hypertension; Losartan; Chlorthalidone; Amlodipine; Blood Pressure; Hypotension; Double-Blind Method; Drug Therapy, Combination; Treatment Outcome
PubMed: 37095689
DOI: 10.1111/jch.14656 -
Perspectives in Clinical Research 2022Diabetes mellitus is a chronic noncommunicable disease, and hypertension (HT) is the most common comorbidity which affects their quality of life (QoL).
BACKGROUND
Diabetes mellitus is a chronic noncommunicable disease, and hypertension (HT) is the most common comorbidity which affects their quality of life (QoL).
AIM
The aim of the study was to assess the effects of antihypertensive agents (viz., amlodipine, ramipril, telmisartan, and ramipril with telmisartan) on the blood pressure (BP) and QoL.
METHODOLOGY
It was an open-labeled prospective intention-to-treat study done in diabetic hypertensive patients (/2016/10). Patients were randomly assigned antihypertensive agents, namely, amlodipine, ramipril, telmisartan, and a combination of ramipril with telmisartan (RT) in four groups. They were evaluated for BP, blood sugar level, and QoL at baseline and 24 week.
RESULTS
After 24 weeks of therapy, systolic BP (SBP) and diastolic BP (DBP) were significantly reduced in all groups. In amlodipine, there was a mean percentage fall of SBP by 15.85% (confidence interval [CI]: 21.38-28.13) and DBP by 11.22% (CI: 8.41-12.70); in ramipril - 14.4% (CI: 18.61-25.15) and 12.4% (CI 8.88-13.99); telmisartan - 18.4% (CI: 24.89-10.79) and 14.6% (CI 10.79-16.24); and in RT group, SBP 17.7% (CI: 23.38-29.18) and DBP 12.4% (CI: 9.05-13.02). QoL score increased by 30.56% (CI: 14.30-10.90), 30.94% (CI: 14.21-10.68), 28.07% (CI: 14.89-11.20), and 28.84% (CI: 15.49-11.77), in respective groups ( < 0.0001, each). However, they were nonsignificant between the study groups ( > 0.05).
CONCLUSION
Amlodipine, ramipril, telmisartan, and a combination of RT are equally effective to improve BP and QoL among diabetic hypertensive patients. However, amlodipine and telmisartan lacked in dry cough and more tolerable than the ramipril and RT therapy. Henceforth, amlodipine and telmisartan are better choice to control HT among DM patients.
PubMed: 35928647
DOI: 10.4103/picr.PICR_15_20