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Revue Medicale de Liege Sep 2017The fixed association of atorvastatin, perindopril and amlodipine was recently launched by the firm SERVIER under the name of Lipertance®. It is the first fixed... (Review)
Review
The fixed association of atorvastatin, perindopril and amlodipine was recently launched by the firm SERVIER under the name of Lipertance®. It is the first fixed association of a statin, an ACE inhibitor and a calcium blocker present on the Belgian market to handle the risk factors that are hypertension and dyslipidemia which can be used both in primary and secondary cardiovascular prevention. The interests of such a triple combined therapy are many in terms of morbimortality reduction, as observed in ASCOT trial. Besides these results, the association of these three agents gives probably a synergic effect, which would be more effective to protect both heart and vessels. Moreover, a fixed association will improve treatment compliance and adherence, which are generally quite poor in the management of cardiovascular risk factors. Lipertance® is available with three different doses : 20/5/5 mg, 20/10/5 mg and 40/10/10 mg, respectively for atorvastatin, perindopril and amlodipine. Contraindications and side effects are the same as each component of this association and are well known.
Topics: Amlodipine; Atorvastatin; Cardiovascular Diseases; Clinical Trials as Topic; Drug Combinations; Humans; Hypertension; Perindopril; Risk Factors
PubMed: 28892318
DOI: No ID Found -
BMC Cardiovascular Disorders Jul 2017To evaluate cardiovascular function in boys with Duchenne (DMD) and Becker (BMD) muscular dystrophy, using cardiac magnetic resonance (CMR).
BACKGROUND
To evaluate cardiovascular function in boys with Duchenne (DMD) and Becker (BMD) muscular dystrophy, using cardiac magnetic resonance (CMR).
METHODS
This is a single point cross sectional study of twenty-four boys with genetically ascertained DMD, and 10 with BMD, aged 10.5 ± 1.5 years (range 9-13), were prospectively evaluated by a 1.5 T system and compared with those of age-sex matched controls. The DMD patients were divided in 2 groups. Group A (N = 12) were under treatment with both deflazacort and perindopril, while Group B (n = 12) were under treatment with deflazacort, only. BMD patients did not take any medication. Biventricular function was assessed using a standard SSFP sequence. Late gadolinium enhancement (LGE) was assessed from T1 images taken 15 min after injection of 0.2 mg/Kg gadolinium DTPA using a 3D-T1-TFE sequence.
RESULTS
Group A and BMDs were asymptomatic with normal ECG, 24 h ECG recording and echocardiogram. Group B were asymptomatic but 6/12 had abnormal ECG and mildly impaired LVEF. Their 24 h ECG recording revealed supraventricular and ventricular extrasystoles (all at 12-13 yrs). LV indices in Group A and BMD did not differ from those of controls. However, LV indices in Group B were significantly impaired compared with controls, Group A and BMDs (p < 0.001). An epicardial LGE area = 3 ± 0.5% of LV mass was identified in the posterolateral wall of LV only in 6/12 patients of Group B, but in not in any BMD or Group A.
CONCLUSION
Children with either BMD or DMD under treatment with both deflazacort and perindopril present preserved LV function and lack of LGE. However, further large scale multicenter studies are warranted to confirm these data, including further CMR mapping approaches.
Topics: Adolescent; Angiotensin-Converting Enzyme Inhibitors; Asymptomatic Diseases; Case-Control Studies; Child; Contrast Media; Cross-Sectional Studies; Echocardiography; Electrocardiography; Gadolinium DTPA; Heart Diseases; Humans; Magnetic Resonance Imaging; Male; Muscular Dystrophy, Duchenne; Perindopril; Pregnenediones; Protective Agents; Time Factors; Treatment Outcome; Ventricular Function, Left; Ventricular Function, Right
PubMed: 28738778
DOI: 10.1186/s12872-017-0627-x -
International Journal of Molecular... Jan 2017This paper presents the results obtained after studying the thermal stability and decomposition kinetics of perindopril erbumine as a pure active pharmaceutical... (Comparative Study)
Comparative Study
This paper presents the results obtained after studying the thermal stability and decomposition kinetics of perindopril erbumine as a pure active pharmaceutical ingredient as well as a solid pharmaceutical formulation containing the same active pharmaceutical ingredient (API). Since no data were found in the literature regarding the spectroscopic description, thermal behavior, or decomposition kinetics of perindopril, our goal was the evaluation of the compatibility of this antihypertensive agent with the excipients in the tablet under ambient conditions and to study the effect of thermal treatment on the stability of perindopril erbumine. ATR-FTIR (Attenuated Total Reflectance Fourier Transform Infrared) spectroscopy, thermal analysis (thermogravimetric mass curve (TG-thermogravimetry), derivative thermogravimetric mass curve (DTG), and heat flow (HF)) and model-free kinetics were chosen as investigational tools. Since thermal behavior is a simplistic approach in evaluating the thermal stability of pharmaceuticals, in-depth kinetic studies were carried out by classical kinetic methods (Kissinger and ASTM E698) and later with the isoconversional methods of Friedman, Kissinger-Akahira-Sunose and Flynn-Wall-Ozawa. It was shown that the main thermal degradation step of perindopril erbumine is characterized by activation energy between 59 and 69 kJ/mol (depending on the method used), while for the tablet, the values were around 170 kJ/mol. The used excipients (anhydrous colloidal silica, microcrystalline cellulose, lactose, and magnesium stearate) should be used in newly-developed generic solid pharmaceutical formulations, since they contribute to an increased thermal stability of perindopril erbumine.
Topics: Drug Compounding; Drug Stability; Kinetics; Perindopril; Spectroscopy, Fourier Transform Infrared; Temperature; Thermogravimetry
PubMed: 28098840
DOI: 10.3390/ijms18010164 -
Journal of the American Heart... Mar 2016
Topics: Angiotensin-Converting Enzyme Inhibitors; Coronary Artery Disease; Cost-Benefit Analysis; Humans; Perindopril; Pharmacogenetics
PubMed: 27021567
DOI: 10.1161/JAHA.116.003440 -
Biomedicine & Pharmacotherapy =... May 2023This study investigated the reno-protective effects of a highly selective ATR agonist peptide, β-ProAng III in a mouse model of acute kidney injury (AKI).
BACKGROUND AND PURPOSE
This study investigated the reno-protective effects of a highly selective ATR agonist peptide, β-ProAng III in a mouse model of acute kidney injury (AKI).
METHODS
C57BL/6 J mice underwent either sham surgery or unilateral kidney ischemia-reperfusion injury (IRI) for 40 min. IRI mice were treated with either β-ProAng III or perindopril and at 7 days post-surgery the kidneys analysed for histopathology and the development of fibrosis and matrix metalloproteinase (MMP)-2 and -9 activity. The association of the therapeutic effects of β-ProAng III with macrophage number and phenotype was determined in vivo and in vitro.
KEY RESULTS
Decreased kidney tubular injury, interstitial matrix expansion and reduced interstitial immune cell infiltration in IRI mice receiving β-ProAng III treatment was observed at day 7, compared to IRI mice without treatment. This correlated to reduced collagen accumulation and MMP-2 activity in IRI mice following β-ProAng III treatment. FACS analysis showed a reduced number and proportion of CD45CD11bF4/80 macrophages in IRI kidneys in response to β-ProAng III, correlating with a significant increase in M2 macrophage markers and decreased M1 markers at day 3 and 7 post-IR injury, respectively. In vitro analysis of cultured THP-1 cells showed that β-ProAng III attenuated lipopolysaccharide (LPS)-induced tumour necrosis factor-α (TNF-α) and interleukin (IL)- 6 production but increased IL-10 secretion, compared to LPS alone.
CONCLUSION
Administration of β-ProAng III via mini-pump improved kidney structure and reduced interstitial collagen accumulation, in parallel with an alteration of macrophage phenotype and anti-inflammatory cytokine release, therefore mitigating the downstream progression of ischemic AKI.
Topics: Mice; Animals; Lipopolysaccharides; Mice, Inbred C57BL; Kidney; Acute Kidney Injury; Collagen; Reperfusion Injury; Reperfusion
PubMed: 36948137
DOI: 10.1016/j.biopha.2023.114556 -
Biomedicine & Pharmacotherapy =... Mar 2021To evaluate the bioequivalence between test and reference formulations of perindopril tert-butylamine under fasting and fed conditions and to assess their... (Comparative Study)
Comparative Study Randomized Controlled Trial
Bioequivalence study of two perindopril tert-butylamine tablet formulations in healthy Chinese subjects under fasting and fed conditions: A randomized, open-label, single-dose, crossover trial.
BACKGROUND
To evaluate the bioequivalence between test and reference formulations of perindopril tert-butylamine under fasting and fed conditions and to assess their pharmacokinetic (PK) and safety profiles.
METHOD
A randomized, open-label, single-dose, crossover trial was conducted in healthy Chinese subjects. Test or reference perindopril tert-butylamine tablets (4 mg) were randomly given to subjects under fasting (2-period crossover, with an administration sequence of test tablet (T), reference tablet (R) or RT) and fed (4-period crossover, with an administration sequence of TRTR or RTRT) conditions, while each single administration was followed by a 14-day washout period. The plasma concentrations and corresponding non-compartmental PK parameters of perindopril and perindoprilat were determined. The two formulations were considered to be bioequivalent if the 90 % confidence intervals (CIs) of the geometric mean (GM) ratio (test/reference) for C, AUC, and AUC (perindopril) was both within the range of 80-125 %. Safety assessments including vital signs, physical examination, laboratory examination, 12-lead ECG and reports of treatment emergent adverse events (TEAEs) were carefully documented.
RESULTS
A total of 64 subjects (32 in each trial) were randomized and all completed the trials. Regardless of fasting or fed trials, the PK characteristics of perindopril and perindoprilat for the test formulation were similar to those of the reference formulation (all P > 0.05). The 90 % CIs of the geometric mean (GM) ratio for C, AUC and AUC, respectively, were 92.86-106.81 %, 98.44-102.88 % and 98.48-103.02 % under the fasting condition and 90.64-110.04 %, 96.95-101.90 % and 96.83-101.78 % under the fed condition, which were both within the pre-specified range of 80-125 %. A total of 10 (31.3 %) fasted subjects and 11 (34.4 %) fed subjects experienced 11 and 24 TEAEs, respectively, all of which were within the severity of grade 1. The incidence of TEAEs and drug-related TEAEs were similar between test and reference formulations (all P > 0.05) and no serious TEAEs or deaths occurred during the trials.
CONCLUSIONS
The test and reference formulations of perindopril tert-butylamine tablets (4 mg) were bioequivalent and well tolerated in healthy Chinese subjects under fasting and fed conditions.
Topics: Administration, Oral; Adult; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Butylamines; China; Cross-Over Studies; Drug Compounding; Drugs, Generic; Fasting; Female; Humans; Male; Perindopril; Postprandial Period; Tablets; Therapeutic Equivalency; Young Adult
PubMed: 33433351
DOI: 10.1016/j.biopha.2021.111221 -
Circulation Journal : Official Journal... Jan 2018Levels of triglycerides and free fatty acids (FFAs) are elevated in patients with diabetes and may contribute to endothelial dysfunction through renin-angiotensin system...
BACKGROUND
Levels of triglycerides and free fatty acids (FFAs) are elevated in patients with diabetes and may contribute to endothelial dysfunction through renin-angiotensin system (RAS) activation and oxidative stress. The present study investigated how systemic FFA loading affected myocardial microcirculation during hyperemia via RAS.Methods and Results:Eight healthy men received candesartan, perindopril, or a placebo for 2 days in a double-blind crossover design, and then myocardial microcirculation during hyperemia induced by a 2-h infusion of lipid/heparin was assessed using dipyridamole stress-myocardial contrast echocardiography (MCE). Leukocyte activity and hemorheology were also assessed ex vivo using a microchannel flow analyzer, serum levels of oxidative stress markers, and IκB-α expression in mononuclear cells. Serum FFA elevation by the infusion of lipid/heparin significantly decreased myocardial capillary blood velocity and myocardial blood flow during hyperemia. Both candesartan and perindopril significantly prevented the FFA-induced decrease in capillary blood velocity and myocardial blood flow during hyperemia. Systemic FFA loading also caused an increase in the number of adherent leukocytes and prolonged the whole blood passage time. These effects were blocked completely by candesartan and partially by perindopril. Both agents prevented the FFA-induced enhancement of oxidative stress and IκB-α degradation in mononuclear cells.
CONCLUSIONS
Both candesartan and perindopril can prevent FFA-induced myocardial microcirculatory dysfunction during hyperemia via modulation of leukocyte activation and microvascular endothelial function.
Topics: Adult; Benzimidazoles; Biphenyl Compounds; Coronary Circulation; Cross-Over Studies; Double-Blind Method; Endothelium, Vascular; Fatty Acids, Nonesterified; Humans; Hyperemia; Lipids; Lymphocyte Activation; Male; Microcirculation; NF-KappaB Inhibitor alpha; Oxidative Stress; Perindopril; Renin-Angiotensin System; Tetrazoles; Young Adult
PubMed: 28954968
DOI: 10.1253/circj.CJ-17-0809 -
Frontiers in Cardiovascular Medicine 2021Adropin (ADR) is a novel regulatory polypeptide and has important effects on energy metabolism in the heart. However, it is still unclear whether ADR can relieve...
Adropin (ADR) is a novel regulatory polypeptide and has important effects on energy metabolism in the heart. However, it is still unclear whether ADR can relieve ventricular remodeling in DCM. Therefore, this study was conducted to assess the effect of ADR on myocardial fibrosis in DCM rats. Twenty Wistar rats were randomly assigned into four groups: healthy control group (CON), DCM model group (DCM), DCM model treated with ADR group (ADR) and DCM model treated with perindopril group (PER). Collagen volume fraction (CVF) and perivascular collagen area (PVCA) were calculated. Diastolic function was assessed by echocardiography. The mitochondrial membrane potential assay was conducted by Rhodamine 123 staining. The protein expression levels of Col I, Col III, Mitofusin-1, Mitofusin-2 and Drp1 were evaluated using western blot. Compared to CON group, CVF, PVCA and the relative protein expression of Col I, Col III and Drp1 increased in DCM group. And the relative expression of Mitofusin-1 and Mitofusin-2 proteins decreased. During our investigations, CVF, PVCA and the relative protein expression of Col I, Col III and Drp1 decreased in ADR treated rats compared to DCM group. The diastolic function was elevated in ADR group. The fluorescence of Rhodamine 123 and the expression of Mitofusin-1 and Mitofusin-2 also increased in ADR group. Our study demonstrated that ADR could alleviate myocardial fibrosis and improve diastolic function in DCM rats. ADR may be a putative candidate for the treatment of DCM.
PubMed: 34322528
DOI: 10.3389/fcvm.2021.688586 -
Clinical and Translational Science Nov 2021Previous studies showed that postmenopausal women are more likely to have poorly controlled hypertension than men of the same age. Whether this is caused by inadequate...
Previous studies showed that postmenopausal women are more likely to have poorly controlled hypertension than men of the same age. Whether this is caused by inadequate treatment or poor response to antihypertensive agents remains unknown. The aim of this study is to analyze treatment response to the most potent renin angiotensin aldosterone system (RAAS) inhibitor perindopril in different age categories in women and men. Individual patient data were used from the combined European Trial on Reduction of Cardiac Events With Perindopril (EUROPA), Perindopril Protection Against Recurrent Stroke Study (PROGRESS), and Action in Diabetes and Vascular disease: Preterax and Diamicron-MR Controlled Evaluation (ADVANCE) trials, which include patients with vascular disease (n = 29,463). We studied the relative and absolute changes in systolic blood pressure (SBP) and diastolic blood pressure (DBP) during a 4-week run-in phase in which all patients were treated with the perindopril-based treatment in different age categories. In total, 8366 women and 21,097 men were included in the analysis. Women greater than 65 years of age showed a significantly smaller blood pressure reduction after perindopril treatment (2.8 mmHg [95% confidence interval {CI} = 0.1-5.5] less reduction compared to women ≤45 years, p = 0.039). In men, the SBP reduction after perindopril in patients greater than 55-65 and greater than 65 years was lower compared to the age category less than or equal to 45 years (adjusted mean difference >55-65: 2.8 mmHg [95% CI = 1.8-3.7], p < 0.001, >65: 3.7 mmHg [95% CI = 2.7-4.7], p < 0.001). A trend of less blood pressure reduction was seen with ageing in both men and women (p < 0.001). To conclude, we observed that in both women and men the perindopril leads to less SBP reduction with increasing age, whereas the DBP reduction increases with age. More research is needed to determine whether it would be beneficial to use age-adjusted perindopril dosages.
Topics: Adult; Age Factors; Aged; Antihypertensive Agents; Blood Pressure; Female; Humans; Male; Middle Aged; Outcome Assessment, Health Care; Perindopril
PubMed: 34080302
DOI: 10.1111/cts.13076 -
Biomedicine & Pharmacotherapy =... Apr 2023The hormone, relaxin (RLX), exerts various organ-protective effects independently of etiology. However, its complex two-chain and three disulphide bonded structure is a...
The single-chain relaxin mimetic, B7-33, maintains the cardioprotective effects of relaxin and more rapidly reduces left ventricular fibrosis compared to perindopril in an experimental model of cardiomyopathy.
The hormone, relaxin (RLX), exerts various organ-protective effects independently of etiology. However, its complex two-chain and three disulphide bonded structure is a limitation to its preparation and affordability. Hence, a single chain-derivative of RLX, B7-33, was developed and shown to retain the anti-fibrotic effects of RLX in vitro and in vivo. Here, we determined whether B7-33 could retain the other cardioprotective effects of RLX, and also compared its therapeutic efficacy to the ACE inhibitor, perindopril. Adult male 129sv mice were subjected to isoprenaline (ISO; 25 mg/kg/day, s.c)-induced cardiomyopathy, then s.c-treated with either RLX (0.5 mg/kg/day), B7-33 (0.25 mg/kg/day; equivalent dose corrected for MW) or perindopril (1 mg/kg/day) from days 7-14 post-injury. Control mice received saline instead of ISO. Changes in animal body weight (BW) and systolic blood pressure (SBP) were measured weekly, whilst cardiomyocyte hypertrophy and measures of vascular dysfunction and rarefaction, left ventricular (LV) inflammation and fibrosis were assessed at day 14 post-injury. ISO-injured mice had significantly increased LV inflammation, cardiomyocyte hypertrophy, fibrosis, vascular rarefaction and aortic contractility in the absence of any changes in BW or SBP at day 14 post-injury. Both B7-33 and RLX equivalently reduced LV fibrosis and normalised the ISO-induced LV inflammation and cardiomyocyte hypertrophy, whilst restoring blood vessel density and aortic contractility. Comparatively, perindopril lowered SBP and the ISO-induced LV inflammation and vascular rarefaction, but not fibrosis or hypertrophy. As B7-33 retained the cardioprotective effects of RLX and provided rapid-occurring anti-fibrotic effects compared to perindopril, it could be considered as a cost-effective cardioprotective therapy.
Topics: Mice; Animals; Male; Perindopril; Relaxin; Microvascular Rarefaction; Cardiomyopathies; Models, Theoretical; Inflammation; Hypertrophy
PubMed: 36753958
DOI: 10.1016/j.biopha.2023.114370