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Cureus Jul 2022The effect of antihypertensive drugs, especially drugs modulating the renin-angiotensin-aldosterone-system (RAAS), on neurodegenerative diseases still needs to be...
The effect of antihypertensive drugs, especially drugs modulating the renin-angiotensin-aldosterone-system (RAAS), on neurodegenerative diseases still needs to be investigated. This study aimed to compare the effects of three different antihypertensive drugs (telmisartan, perindopril, and nebivolol) on neuroprotection and acetylcholine (ACh) levels against lipopolysaccharide (LPS)-induced injury in a differentiated SH-SY5Y cell line. Cells were treated with retinoic acid for differentiation to a neuronal phenotype. LPS 20 (μg/mL) was applied to the cells for one hour. Then, the cells were treated with 1, 5, and 10 µg/mL concentrations of telmisartan, perindopril, and nebivolol separately for 24 hours, except for the control and LPS alone groups. Cell viability was evaluated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. ACh levels were analyzed using an enzyme immunosorbent assay in the culture medium. Tumor necrosis factor-alpha (TNF-α), interleukin 1 beta (IL-1β), and nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) expressions were evaluated using western blot analysis. Telmisartan demonstrated the highest cell viability against LPS-induced injury, whereas the protective effect of perindopril was moderate. Nebivolol showed no neuroprotective effect. The protective effect of 10-µg/mL telmisartan was superior to 10 µg/mL perindopril (p=0.006), 5 µg/mL perindopril (p=0.001), 1 µg/mL perindopril (p=0.001), and 1, 5, and 10 µg/mL nebivolol (p<0.001). Among all the study drugs, only telmisartan provided a statistically significant increase in ACh levels after LPS-induced injury. Additionally, the administration of telmisartan provided a concentration-dependent reduction in TNF-α, IL-1β, and NFκB expression against LPS-induced neuroinflammation. These findings suggest that telmisartan has a superior neuroprotective effect against LPS-induced injury in neuron-like cells compared with both perindopril and nebivolol.
PubMed: 36051740
DOI: 10.7759/cureus.27429 -
Journal of Chromatography. B,... Apr 2021Lots of studies showed the combination therapy of perindopril, indapamide and amlodipine could increase BP lowering efficacy and the benefits of high-risk patients. To... (Randomized Controlled Trial)
Randomized Controlled Trial
Lots of studies showed the combination therapy of perindopril, indapamide and amlodipine could increase BP lowering efficacy and the benefits of high-risk patients. To evaluate potential pharmacokinetic interaction, a simultaneous UPLC-MS/MS quantification method of perindopril, perindoprilat and indapamide in human plasma was developed and validated. The plasma samples were prepared by solid phase extraction, and then separated on an X-terra MS C (2.1 mm × 150 mm, 3.5 μm) with isocratic elution. The ion transitions at m/z 369.165 → 172.000 (perindopril), m/z 341.146 → 170.112 (perindoprilat), m/z 366.010 → 132.100 (indapamide), m/z 389.120 → 206.200 (S10211-1, IS1) and m/z 394.080 → 160.200 (S1641, IS2) were monitored under the positive ion mode of electrospray ionization with multiple reaction monitoring. This method exhibited great sensitivity, linearity, accuracy, and precision for the determination of perindopril, perindoprilat and indapamide over the range of 0.250-50.0 ng/mL. The average extraction recovery of perindopril, perindoprilat and indapamide samples at low, medium, and high concentration levels were between 85.9% and 93.6%, respectively. The stability of analytes over different storage and processing conditions in the whole study was also validated. The method is fast, accurate, sensitive and reproducible, which is suitable for the detection of the concentration of perindopril, perindoprilat and indapamide in human plasma.
Topics: Chromatography, High Pressure Liquid; Cross-Over Studies; Drug Combinations; Humans; Indapamide; Indoles; Linear Models; Male; Perindopril; Reproducibility of Results; Sensitivity and Specificity; Solid Phase Extraction; Tandem Mass Spectrometry
PubMed: 33706186
DOI: 10.1016/j.jchromb.2021.122585 -
Expert Review of Clinical Pharmacology Jan 2024Although a growing number of observational studies suggest that angiotensin-converting enzyme inhibitors (ACEIs) intake may be a risk factor for psoriasis, evidence is...
BACKGROUND
Although a growing number of observational studies suggest that angiotensin-converting enzyme inhibitors (ACEIs) intake may be a risk factor for psoriasis, evidence is still insufficient to draw definitive conclusions.
RESEARCH DESIGN AND METHODS
Drug-targeted Mendelian randomization (DTMR) was used to analyze the causality between genetic proxied ACEIs and psoriasis. Furthermore, we performed a disproportionality analysis based on the FDA adverse event reporting system (FAERS) database to identify more suspicious subclasses of ACEIs.
RESULTS
Using two kinds of genetic proxy instruments, the present DTMR research identified genetic proxied ACEIs as risk factors for psoriasis. Furthermore, our disproportionality analysis revealed that ramipril, trandolapril, perindopril, lisinopril, and enalapril were associated with the risk of psoriasis, which validates and refines the findings of the DTMR.
CONCLUSIONS
Our integrative study verified that ACEIs, especially ramipril, trandolapril, perindopril, lisinopril, and enalapril, tended to increase the risk of psoriasis statistically.
Topics: Humans; Angiotensin-Converting Enzyme Inhibitors; Ramipril; Lisinopril; Perindopril; Pharmacovigilance; Mendelian Randomization Analysis; Enalapril; Psoriasis
PubMed: 38078460
DOI: 10.1080/17512433.2023.2292605 -
Possible combined effect of perindopril and Azilsartan in an experimental model of dementia in rats.Saudi Pharmaceutical Journal : SPJ :... May 2020Renin-angiotensin system exerted deleterious effects on learning and cognitive functions through different mechanisms. The present study has been designed to evaluate...
Renin-angiotensin system exerted deleterious effects on learning and cognitive functions through different mechanisms. The present study has been designed to evaluate the protective effect of perindopril and azilsartan as monotherapy or in combination on aluminum chloride (AlCl) induced neurobehavioral and pathological changes in Alzheimeric rats. Male Wistar rats were divided into nine groups (n = 6); negative control, AlCl3 treated, vehicle, AlCl3 and Azilsartan (3.5 mg/kg, 7 mg/kg) co-treated, AlCl3 and perindopril (0.5 mg/kg, 1 mg/kg) co-treated, AlCl3 and (Azilsartan 3.5 mg/kg + perindopril 0.5 mg/kg), and AlCl3 and (Azilsartan 7 mg/kg + perindopril 1 mg/kg), all groups were treated for consecutive 60 days. Then, memory function was evaluated by the Y- maze test. Amyloid Peptide - 42 (Aβ-42), Acetylcholinesterase (AChE), Malondialdehyde (MDA), Tumor necrosis factor (TNF-α) and Nitric Oxide (NO) levels in the hippocampus were assessed with (ELISA) kits. The histopathological studies of the hippocampal dentate gyrus (DG) and Cornu Ammonis-3 (CA3) were also performed. Oral administration of either azilsartan and perindopril alone or in combined for 60 days have shown; improvement of cognitive function, significant reduction in the hippocampal levels of Aβ-42, Acetylcholinesterase, Malondialdehyde (MDA), Tumor necrosis factor (TNF-α) and reserved most of histopathological changes in dentate gyrus (DG) and Cornu Ammonis-3 (CA3) that mediated by Alcl. Our behavioral, biochemical, and histopathological studies indicate that perindopril and azilsartan have neuroprotective effects on the AD model of rats induced by AlCl, suggesting that perindopril and azilsartan may be a candidate drugs for the treatment of AD.
PubMed: 32435138
DOI: 10.1016/j.jsps.2020.03.009 -
Bratislavske Lekarske Listy 2023We performed this meta-analysis determining the antihypertensive effect of telmisartan versus perindopril in patients with essential hypertension. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
We performed this meta-analysis determining the antihypertensive effect of telmisartan versus perindopril in patients with essential hypertension.
BACKGROUND
The comparison of antihypertensive effects between telmisartan and perindopril were controversial.
METHODS
Pubmed, Web of Science, and Cochrane Central were searched for all published studies.
RESULTS
The antihypertensive effects were assessed in 753 patients included in 7 trials with a mean follow-up of 20 ± 16 weeks. There was no significant difference between telmisartan and perindopril in reduction of systolic blood pressure (SBP, weighted mean differences (WMD) 0.02 (95% confidence interval (CI), ‒2.78, 2.81) mm Hg, p > 0.05). The reduction of diastolic BP (DBP) treated with telmisartan was greater than perindopril in these patients (WMD ‒2.05 (95% CI, ‒2.60, ‒1.49) mm Hg, p < 0.001). Considering the effects of different doses on BP reduction, a sub-analysis was performed. The reduction of DBP treated with 40 mg/day telmisartan was greater than 4‒5 mg/day perindopril (WMD ‒2.18 (95% CI, ‒2.83, ‒1.53) mm Hg, p 0.05).
CONCLUSION
The reduction of DBP is greater treated with telmisartan than perindopril in patients with essential hypertension (Tab. 2, Fig. 4, Ref. 34). Text in PDF www.elis.sk Keywords: essential hypertension, blood pressure, telmisartan, perindopril, meta-analysis.
Topics: Humans; Antihypertensive Agents; Telmisartan; Perindopril; Benzimidazoles; Hypertension; Essential Hypertension
PubMed: 36876369
DOI: 10.4149/BLL_2023_058 -
Advances in Therapy Jan 2022The combination of angiotensin-converting enzyme inhibitors and beta-blockers is recommended in a wide range of patients with hypertension, including those with stable... (Observational Study)
Observational Study
Concomitant Treatment of Hypertensive Patients with Bisoprolol and Perindopril in Routine Clinical Practice: A Post Hoc Analysis of the CONFIDENCE II, PROTECT I, and PROTECT III Observational Studies.
INTRODUCTION
The combination of angiotensin-converting enzyme inhibitors and beta-blockers is recommended in a wide range of patients with hypertension, including those with stable coronary artery disease and/or elevated heart rate. This post hoc analysis of three observational studies provides effectiveness and safety data on treatment with perindopril on top of bisoprolol-based therapy, in routine clinical practice.
METHODS
Data were analyzed from three open-label, prospective, multicenter, observational studies of Canadian patients with mild-to-moderate hypertension, which shared the same inclusion and exclusion criteria, treatment duration, and primary outcome. This post hoc analysis focused on the subpopulation of patients treated with perindopril on top of bisoprolol-based therapy. All patients were followed for 16 weeks and underwent baseline, week 4, and week 16 visits. Primary outcomes were mean changes in blood pressure (BP) and proportion of patients achieving BP control (< 140/90 mmHg) in the full analysis set (FAS).
RESULTS
A total of 845 patients (mean age 68.3 ± 11.3 years, mean baseline BP 151.5/86.0 mmHg) were analyzed in the FAS. After 16 weeks, mean SBP/DBP decreased by - 20.4/- 9.8 mmHg with statistically significant reductions observed at all visits in all three studies allowing 78% of patients to achieve the BP treatment goal. No statistically significant changes in heart rate were observed and no serious adverse events reported. The most frequent doses of bisoprolol and perindopril were 5 + 4 mg (34.9%), followed by 5 + 8 mg (16.9%), and 2.5 + 4 mg (12.5%).
CONCLUSION
The addition of perindopril on top of bisoprolol-based therapy in patients with mild-to-moderate hypertension was associated with significant reductions in BP compared with baseline and with achievement of BP targets in the majority of patients. The results suggest this strategy is safe and effective for use in routine clinical practice.
Topics: Aged; Antihypertensive Agents; Bisoprolol; Blood Pressure; Canada; Drug Combinations; Humans; Hypertension; Middle Aged; Perindopril; Prospective Studies; Treatment Outcome
PubMed: 34755324
DOI: 10.1007/s12325-021-01958-6 -
Cellular and Molecular Biology... Sep 2023To uncover the potential effect of Perindopril on cardiac fibrosis caused by pressure overload and the underlying mechanism. Cardiac fibrosis model in mice was...
To uncover the potential effect of Perindopril on cardiac fibrosis caused by pressure overload and the underlying mechanism. Cardiac fibrosis model in mice was established by TAC method. Mice were assigned into sham group, TAC group, 2 mg/kg Perindopril group (Per (2 mg/kg)) and 8 mg/kg Perindopril group (Per (8 mg/kg)). Cardiac structure changes were assessed by measuring HW/BW, HW/TBL, LW/BW and LW/TBL in each group. Echocardiography was performed to assess mouse cardiac function by recording EF, LVIDd, IVSd and LVPWd. Relative levels of fibrosis markers were determined. AngII content was examined by ELISA. Besides, mRNA levels of key genes in the AngII/AT1R pathway were finally detected. TAC induced cardiac insufficiency, left ventricular dilatation, cardiac hypertrophy and myocardial collagen deposition in mice. In addition, fibrosis markers were upregulated in mice of TAC group. Perindopril markedly reversed TAC-induced pathological changes in cardiac structure and function of mice. Meanwhile, Perindopril dose-dependently reversed the upregulated genes in the AngII/AT1R pathway. Perindopril improves cardiac fibrosis induced by pressure overload through activating the AngII/AT1R pathway.
Topics: Mice; Animals; Perindopril; Heart; Cardiomegaly; Cardiomyopathies; Myocardium; Fibrosis; Mice, Inbred C57BL; Disease Models, Animal
PubMed: 37807306
DOI: 10.14715/cmb/2023.69.9.36 -
The Chinese Journal of Physiology 2023The purpose of this study was to elucidate the therapeutic effect of different antihypertensive drugs (amlodipine and perindopril) on hypertension induced by apatinib...
Comparison of antihypertensive drugs amlodipine and perindopril on blood pressure variability after long-term treatment of hypertension induced by apatinib and bevacizumab.
The purpose of this study was to elucidate the therapeutic effect of different antihypertensive drugs (amlodipine and perindopril) on hypertension induced by apatinib and bevacizumab. Sixty patients with hypertension treated with apatinib or bevacizumab were selected and divided into two groups: one group was treated with amlodipine and the other group was treated with perindopril. Before and after treatment, the dynamic blood pressure (BP) measurement (systolic BP [SBP] and diastolic BP [DBP]), echocardiography (left ventricular end-diastolic diameter, interventricular septal thickness [IVST], left ventricular posterior wall thickness [LVPWT], and left atrial diameter [LAD]), and detection of nitric oxide (NO) content in venous blood were performed. In the amlodipine group, the 24hSBP, 24hSSD, 24hSCV, daytime mean SBP (dSBP), daytime mean SSD (dSSD), daytime mean SBP CV, night mean SBP (nSBP), night mean SSD, 24hDBP, 24hDSD, 24 h DBP CV, daytime mean DBP (dDBP), daytime mean DSD (dDSD), daytime mean DBP CV, night mean DBP (nDBP), LAD, and LAD index (LADi) after treatment were all lower than before treatment, while NO was higher than before treatment (all P < 0.05). In the perindopril group, the 24hSBP, dSBP, nSBP, 24hDBP, dDBP, nDBP, LAD, LADi, IVST, LVPWT, and left ventricular mass index (LVMI) after treatment were lower than before treatment, and NO level after treatment was higher than before treatment (all P < 0.05). After treatment, the 24hSBP, 24hSSD, dSBP, dSSD, nSBP, 24hDBP, 24hDSD, dDBP, dDSD, nDBP, night mean DSD, and NO were all lower while the LAD, LADi, IVST, LVPWT, and LVMI were higher in the amlodipine group than those in the perindopril group (all P < 0.05). Our study suggests that the SBP and DBP variability of amlodipine in the treatment of hypertension induced by apatinib and bevacizumab is slightly better than that of perindopril, but the effect of perindopril in improving endothelial function indices NO and echocardiographic data is better than that of amlodipine.
Topics: Humans; Antihypertensive Agents; Perindopril; Amlodipine; Blood Pressure; Bevacizumab; Hypertension; Treatment Outcome
PubMed: 37322624
DOI: 10.4103/cjop.CJOP-D-22-00158 -
Vnitrni Lekarstvi 2023The brain is among the target organs of hypertension. Patients with hypertension have a higher risk of developing stroke as well as experiencing a decline in cognitive...
The brain is among the target organs of hypertension. Patients with hypertension have a higher risk of developing stroke as well as experiencing a decline in cognitive functions and dementia. Changes in the white matter and atrophy of the grey matter of the brain induced by high blood pressure develop insidiously since the onset of hypertension, even in young individuals. The effect of high blood pressure on the vessel wall cumulates in time; therefore, hypertension in younger people implies an increased risk of dementia in older age. Hypertension in young age cannot be considered a benign condition. Hypertension in middle age increases the risk of dementia by 61 %. Consistent and early hypertension control can reverse the adverse development towards dementia and lack of self-sufficiency in the patient. Data comparing individual antihypertensive drugs in terms of preventing dementia are scarce. However, renin angiotensin system blockers have been found to protect against Alzheimer's disease more than other classes of antihypertensive drugs. To achieve rapid and effective hypertension control, a combination of antihypertensive drugs is usually required. Using a fixed-dose triple combination of perindopril, indapamide, and amlodipine, blood pressure targets of < 130/80 mm Hg can be achieved within three months in 93 % of patients.
Topics: Middle Aged; Humans; Antihypertensive Agents; Drug Combinations; Hypertension; Amlodipine; Perindopril; Blood Pressure; Dementia
PubMed: 37468294
DOI: 10.36290/vnl.2023.047 -
International Journal of Clinical... Feb 2020To investigate the pharmacokinetic parameters of perindopril and perindoprilat in healthy volunteers, a simple and sensitive UPLC-MS/MS method with isotope-labeled...
OBJECTIVES
To investigate the pharmacokinetic parameters of perindopril and perindoprilat in healthy volunteers, a simple and sensitive UPLC-MS/MS method with isotope-labeled internal standards of perindopril-d4 and perindoprilat-d4 was established and further applied in a bioequivalence study.
MATERIALS AND METHODS
A simple and sensitive UPLC-MS/MS method with isotope-labeled internal standards of perindopril-d4 and perindoprilat-d4 was validated and applied in a single-center, randomized, cross-over, and two-period bioequivalence study. 20 healthy Chinese subjects (16 males and 4 females) were enrolled and had their plasma concentrations of perindopril and perindoprilat quantified and calculated for the pharmacokinetic parameters. After acetonitrile precipitation, the analytes and internal standards were gradient eluted with methanol-acetonitrile-ammonium acetate on an Acquity UPLC BEH C18 (2.1 × 50 mm, 1.7 µm) column. Detection was carried out in a multireaction monitoring mode using positive ionization electrospray mass spectrometry.
RESULTS
The total chromatographic run time was 4 minutes with retention time for perindopril and perindopril-d4 of ~ 1.86 minutes, whereas perindoprilat and perindoprilat-d4 was ~ 1.79 minutes. The calibration curves of perindopril and perindoprilat were linear over 0.4 - 80 ng/mL and 0.2 - 40 ng/mL, respectively. The method was fully validated to meet the requirement for bioassay in accuracy (89.6 - 112.4%), precision (coefficient of variation (CV) ≤ 13.8%), recovery (79.65 - 97.83%), matrix effect (CV ≤ 5.9%), and stability (CV ≤ 10.0%). The 90% confidence intervals (CIs) for the geometric mean ratios of C, AUC, and AUC of perindopril and perindoprilat all fell within the bioequivalence acceptance criteria (80 - 125%). There were no significant differences between the two formulations in terms of t and T of perindopril and perindoprilat. There was no adverse event in this clinical study. Interestingly, it was found that the pharmacokinetics of perindoprilat in 1 subject were significantly different from that of the others which may be associated with genetic diversity.
CONCLUSION
This method was successfully applied to the bioequivalence test of two perindopril tert-butylamine tablets. The two one-sided t-tests showed that these two products were bioequivalent.
Topics: Chromatography, High Pressure Liquid; Cross-Over Studies; Female; Humans; Indoles; Male; Perindopril; Reproducibility of Results; Tablets; Tandem Mass Spectrometry; Therapeutic Equivalency
PubMed: 31845865
DOI: 10.5414/CP203593