Efficacy of fosinopril and amlodipine in pediatric primary hypertension: a single-center observational study.

Objective: Fosinopril and amlodipine are commonly prescribed as first-line pharmacotherapeutic agents for pediatric hypertension, but there is a lack of comparative studies regarding the efficacy of these two drugs. We aimed to evaluate and compare the efficacy of fosinopril and amlodipine monotherapy in pediatric primary hypertension. Methods: This was a single-center, bidirectional observational study. A total of 175 children and adolescents with primary hypertension receiving antihypertensive monotherapy from July 2020 to February 2023 were enrolled. According to antihypertensive drugs, they were divided into the fosinopril group (n = 96) and the amlodipine group (n = 79). Subgroup analysis was performed to compare the efficacy of the two groups in terms of blood pressure (BP) control rates and reductions following a 4-week treatment. Results: After 4 weeks of treatment, both groups achieved significant reductions in systolic BP (SBP) and diastolic BP (DBP) by more than 18 mmHg and 6 mmHg, respectively, with BP control rates of 61.5% in the fosinopril group and 59.5% in the amlodipine group, revealing no significant differences in the antihypertensive efficacy between the two groups except for DBP control rate (FDR adjusted P > 0.05). Further subsequent subgroup analyses revealed that the reductions in SBP and DBP in the fosinopril group were significantly greater than those in the amlodipine group in patients of females and hypo-HDL-cholesterolemia (FDR adjusted P < 0.05), and there was a trend of difference, although not significant, in patients with central obesity and insulin resistance (IR) (FDR adjusted 0.05 < P ≤ 0.1). However, there were no significant differences in treatment efficacy in patients without these characteristics. Furthermore, hypertriglyceridemia did not exhibit a significant association with the difference in treatment efficacy between the two medications (FDR adjusted P > 0.05). Conclusions: Fosinopril and amlodipine monotherapy were both effective in pediatric primary hypertension during a short-term follow-up. Fosinopril may be particularly effective in reducing BP in hypertensive patients of females, central obesity, IR, and hypo-HDL-cholesterolemia. These findings indicate that optimizing antihypertensive medication selection based on the individualized characteristics of children with hypertension may improve the efficacy of antihypertensive treatment.

Babesia BdFE1 esterase is required for the anti-parasitic activity of the ACE inhibitor fosinopril.

Effective and safe therapies for the treatment of diseases caused by intraerythrocytic parasites are impeded by the rapid emergence of drug resistance and the lack of novel drug targets. One such disease is human babesiosis, which is a rapidly emerging tick-borne illness caused by Babesia parasites. In this study, we identified fosinopril, a phosphonate-containing, FDA-approved angiotensin converting enzyme (ACE) inhibitor commonly used as a prodrug for hypertension and heart failure, as a potent inhibitor of Babesia duncani parasite development within human erythrocytes. Cell biological and mass spectrometry analyses revealed that the conversion of fosinopril to its active diacid molecule, fosinoprilat, is essential for its antiparasitic activity. We show that this conversion is mediated by a parasite-encoded esterase, BdFE1, which is highly conserved among apicomplexan parasites. Parasites carrying the L238H mutation in the active site of BdFE1 failed to convert the prodrug to its active moiety and became resistant to the drug. Our data set the stage for the development of this class of drugs for the therapy of vector-borne parasitic diseases.

Effect of fosinopril on angiotensin converting enzyme 2 and vascular endothelial growth factor in diabetic retinopathy mice / 解剖学报

Objective To explore the protective effect of fosinopril (Fos) on streptozotocin ( STZ) induced diabetic retinopatfry( DR) mice and on the expression of angiotensin converting enzyme 2(ACE2) and vascular endothelial growth factor (VEGF) in DR mice. Methods Totally forty-eight healthy male Kunming mice, thirty-six were randomly selected, and a diabetic mouse model induced by STZ was constructed after 6 weeks of high-fat diet. After the successful establishment of the model, the thirty-six mice were randomly divided into three groups: model group, Fos low concentration ( 5 mg/kg) group, and Fos high concentration ( 10 mg/kg) group. The remaining twelve mice were served as the control group. After 8 weeks administration, the bod)' weight and blood glucose level of mice in each group were determined. The change in the retinal structure was verified by HE staining. The serum level of VEGF was measured by ELISA. The expression of ACE2 in the retina tissue was verified by immunohistochemistry. The expression of ACE2 mRNA in diabetic retinopatlry was analyzed by Real-time PCR. The levels of ACE2 and VEGF protein in diabetic retinopatlry were detected by Western blotting. Results Fos ( 5 mg/kg, 10 mg/kg ) reduced significantly the proliferation of neovascularization in the inner boundaiy layer, down-regulated the expression of VEGF in the serum of diabetic mice and promoted the expression of ACE2 in the retina tissue of diabetic mice. In addition, the effect of the high concentration group of Fos had a stronger effect than the lower concentration group (P<0. 0 5 ) . Conclusion Fos has a protective effect on the retinopatlry of diabetic mice. This protective effect ma)' be mediated through the increased expression of ACE2 and the reduction of VEGF expression.

Physicochemical and Stability Evaluation of Topical Niosomal Encapsulating Fosinopril/γ-Cyclodextrin Complex for Ocular Delivery.

This study aimed to develop a chemically stable niosomal eye drop containing fosinopril (FOS) for lowering intraocular pressure. The effects of cyclodextrin (CD), surfactant types and membrane stabilizer/charged inducers on physiochemical and chemical properties of niosome were evaluated. The pH value, average particle size, size distribution and zeta potentials were within the acceptable range. All niosomal formulations were shown to be slightly hypertonic with low viscosity. Span® 60/dicetyl phosphate niosomes in the presence and absence of γCD were selected as the optimum formulations according to their high %entrapment efficiency and negative zeta potential values as well as controlled release profile. According to ex vivo permeation study, the obtained lowest flux and apparent permeability coefficient values confirmed that FOS/γCD complex was encapsulated within the inner aqueous core of niosome and could be able to protect FOS from its hydrolytic degradation. The in vitro cytotoxicity revealed that niosome entrapped FOS or FOS/γCD formulations were moderate irritation to the eyes. Furthermore, FOS-loaded niosomal preparations exhibited good physical and chemical stabilities especially of those in the presence of γCD, for at least three months under the storage condition of 2-8 °C.

Angiotensin-converting enzyme inhibitor for post-transcatheter aortic valve implantation patients: study protocol for a multicenter randomized, open-label blinded endpoint control trial.

BACKGROUND: With the expanded utilization of transcatheter aortic valve implantation (TAVI) to younger and lower surgical risk patients with severe aortic stenosis (AS), optimal medical therapy after TAVI procedure has become the main concern. Renin-angiotensin system inhibitors (RASi) are widely utilized in the area of cardiovascular disease including heart failure and myocardial infarction and revealed the ability to reverse left ventricular (LV) remodeling. Interests have, thus, been drawn in investigating whether the prescription of RASi after the TAVI procedure can prevent or reverse cardiac remodeling and improve long-term clinical outcomes. No recommendation regarding the prescription of RASi after TAVI is proposed yet due to the lack of evidence from randomized controlled trials, especially in the Chinese population. We, therefore, designed this randomized controlled trial to explore the effect of adding fosinopril to standard care in patients who underwent a successful TAVI procedure on the LV remodeling. METHODS: A total of 200 post-TAVI patients from seven academic hospitals across China will be recruited and randomized with a ratio of 1:1 to receive standard care or standard care plus fosinopril. Follow-up visits will take place at 30 days, 3 months, 6 months, 12 months, and 24 months from randomization to assess the clinical symptoms, any adverse events, cardiac function, and quality of life. Cardiac magnetic resonance will be performed at baseline and repeated at the 24-month follow-up visit to assess LV remodeling. DISCUSSION: This study will provide evidence regarding medical therapy for AS patients who underwent TAVI and filling the gap in the Chinese population. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100042266 . Registered on 17 January 2021.

A sensitive and efficient LC-MS/MS method for the bioanalysis of fosinopril diacid from human plasma and its application for a bioequivalence study in humans.

Fosinopril diacid is an angiotensin converting enzyme inhibitor with efficient antihypertensive action. It is an active metabolic product formed in the body from hydrolysis of its prodrug Fosinopril. A sensitive, rapid method with high recovery for Fosinopril diacid from human plasma was developed. Solid-phase extraction technique employing Waters Oasis SPE cartridges gave clean samples with very high recovery of 97%. The analyte along with its internal standard (Benazepril hydrochloride) were chromatographed on an XTerra RP8 column (4.6 × 50 mm, 5 µm) using methanol-ammonium acetate buffer (10 mm; 90:10, v/v) as the mobile phase. A triple quadrupole mass spectrometer equipped with electrospray ionization source operated in the negative ion mode was used for detection. Multiple reaction monitoring scan mode was used for monitoring the transitions from m/z 434.00 → 237.15 for Fosinopril diacid and m/z 423.10 → 174.00 for Benazepril hydrochloride. Beer-Lambert's law was obeyed in the range of 0.50-1,500.00 ng/ml (r = 0.9993). The stability of the drugs in human plasma and in stock solution was proved by performing stability tests as per US Food and Drug Administration guidelines. The method was successfully applied for a bioequivalence study of Fosinopril diacid in 36 healthy, adult, male volunteers under fasting conditions.

Regulation of epithelial mesenchymal transition by the renin-angiotensin system: a role for klotho in renal tubular epithelial cells.

Klotho is a putative aging suppressor gene that is primarily expressed in renal tubular epithelial cells. Its expression has been reported to protect against fibrosis in human chronic kidney disease. However, the roles of klotho in epithelial-mesenchymal transition (EMT) and renal fibrosis are yet to be elucidated. The present study aimed to investigate the putative roles of klotho in angiotensin (Ang) II-induced damage of renal tubular epithelial cells. NRK-52E rat cells were treated with various combinations of Ang II, the Ang-converting enzyme inhibitor fosinopril (Fos) and the Ang II receptor antagonist valsartan (Val). The levels of transforming growth factor (TGF)-ß1, soluble klotho, α-smooth muscle actin (α-SMA) and E-cadherin in NRK-52E culture supernatants were measured using enzyme-linked immunosorbent assays. Furthermore, the mRNA and protein expression of TGF-ß1, klotho, α-SMA and E-cadherin was detected using semiquantitative reverse transcription-polymerase chain reaction, immunocytochemistry and Western blot analysis. The results demonstrated that Ang II inhibited the expression of klotho and E-cadherin, while it upregulated the expression of TGF-ß1 and α-SMA, in NRK52E cells. Fos and/or Val were revealed to enhance klotho and E-cadherin expression, and suppress the expression of TGF-ß1 and α-SMA, compared with the Ang II-only group. Furthermore, a positive linear correlation was detected between the expression of klotho and E-cadherin, while negative linear correlations with klotho expression were detected for TGF-ß1 and α-SMA expression. In conclusion, the expression of klotho was demonstrated to be enhanced following treatment with Fos and Val in Ang II-treated NRK-52E cells. The present results indicate that klotho may be involved in the inhibition of Ang II-induced EMT in renal tubular epithelial cells. Therefore, klotho may serve as a protective factor in renal tubulointerstitial fibrosis and aid the treatment of chronic kidney disease (CKD) patients using precision therapy.

Clinical effect of low-flow oxygen combined with fosinopril on treatment of acute plateau heart disease / 解放军医学杂志

[Abstract] Objective To study the therapeutic effect and responding time of low-flow oxygen combined with fosinopril on treatment of acute plateau heart disease. Methods Ninety young male officers and soldiers, diagnosed as acute plateau heart disease after rushing into the plateau (Ali region of Tibet, 4300 m) from the plain area and admitted to the Shiquanhe Medical Station in Ali Military Division from Sep. 2017 to Apr. 2018, were recruited in present study. All the subjects were randomly divided into 3 groups: group A were treated with low-flow oxygen (2 L/min, 60 min, twice a day), group B were treated with fosinopril (10 mg/d), and group C were treated with low-flow oxygen (2 L/min, 60 min, twice a day) combined with fosinopril (10 mg/d). Echocardiography was performed 2, 4 and 6 weeks after treatment to detect the pulmonary artery inner diameter (PAD), inner diameter of right outflow ventricular tract (ROVT), mean pulmonary arterial pressure (MPAP) and right ventricular Tei index (RV-Tei), the test results were then compared among the 3 groups to evaluate the therapeutic effect. Results Two weeks after treatment, the PAD, ROVT, MPAP and RV-Tei in group C [(21.66±3.49) mm, (25.81±2.33) mm, (22.37±2.78) mmHg and (0.24±0.05)] were significantly lower than in group A and group B [(28.37±3.75) mm and (27.29±2.91) mm; (31.25±5.27) mm and (30.34±5.66) mm; (28.25±4.17) mmHg and (27.11±4.94) mmHg; and (0.33±0.08) and (0.32±0.05)] with statistical differences (P0.05). Four weeks after treatment, the PAD, ROVT, MPAP and RV-Tei in group B and group C [(22.21±1.76) mm and (21.17±1.97) mm; (25.29±3.71) mm and (24.30±1.99) mm; (23.91±2.63) mmHg and (21.03±3.17) mmHg; and (0.23±0.06) and (0.23±0.05)] were significantly lower than in group A [(25.09±3.75) mm; (29.38±3.06) mm; (27.87±3.71) mmHg; and (0.29±0.05)] with statistical differences (P0.05). Six weeks after treatment, for PAD, ROVT, MPAP and RV-Tei no significant difference existed among group A, group B and group C [(22.71±2.86) mm, (21.29±2.56) mm, (20.39±2.03) mm; (24.08±3.51) mm, (23.15±3.08) mm, (23.02±2.31) mm; (23.42±1.79) mmHg, (22.88±2.77) mmHg, (21.72±2.49) mmHg; and (0.23±0.04), (0.22±0.06), (0.22±0.06)], and all the measured values reached normal level. Conclusion Low-flow oxygen combined with fosinopril therapy is more effective in curing acute plateau heart disease, and in preventing right heart failure caused by plateau heart disease.

Simultaneous ultraperformance liquid chromatography/tandem mass spectrometry determination of four antihypertensive drugs in human plasma using hydrophilic-lipophilic balanced reversed-phase sorbents sample preparation protocol.

Therapeutic drug monitoring of angiotensin-converting enzyme inhibitors has a great impact on blood pressure control in patients with heart failure and hepatic and renal impairment. To provide an efficient tool for drug assessment in plasma, a UPLC-MS/MS method was developed for simultaneous determination of benazepril hydrochloride, fosinopril sodium, captopril and hydrochlorothiazide in human plasma samples. Solid phase extraction was applied for sample preparation using OASIS® hydrophilic-lipophilic balanced reversed-phase sorbents cartridges. Chromatographic separation was performed using an Agilent SB-C18 column and methanol-0.1% formic acid in water (95:5, v/v) as mobile phase, at flow rate 0.3 mL/min. Detection was accomplished using a tandem mass spectrometer. The method was validated according to US Food and Drug Administration guidelines. It showed good linearity over concentration ranges 5-400 ng/mL for benazepril hydrochloride, fosinopril sodium and hydrochlorothiazide and 100-3500 ng/mL for captopril. CV% values were <13.92% whereas the mean accuracy ranged from 94.50 to 113.82% for quality control samples and their extraction recoveries ranged from 90.60 to 99.38%. In conclusion, the present study revealed method selectivity and sensitivity; it can be applied for estimation of angiotensin converting enzyme inhibitors and hydrochlorothiazide in human plasma for dose adjustment and therapeutic drug monitoring.

[Choice of an Optimal Blocker of the Renin-Angiotensin-Aldosterone System in Patients With Concomitant Arterial Hypertension and Chronic Obstructive Pulmonary Disease].

OBJECTIVE: to compare hypotensive and pleiotropic effects of angiotensin II receptor blocker (ARB) azilsartan medoxomil (AM) and angiotensin converting enzyme inhibitor (ACEI) fosinopril in patients with concomitant arterial hypertension (AH) and chronic obstructive pulmonary disease (COPD). MATERIALS AND METHODS: We included in this open study 49 patients with concomitant stage I-II AH and COPD. Initially all patients received hydrochlorothiazide (12.5 mg/day) and various ACEI but target blood pressure levels were not achieved, and these ACEI were withdrawn. By method of closed envelopes, the patients were divided into 2 groups. Patients of group 1 were given ARB АМ, of group 2 - ACEI fosinopril. Methods of investigation were repetitive 24­hour ambulatory blood pressure monitoring (ABPM), spirometry, measurement of mean pulmonary artery pressure (mPAP), study of endothelial function by instrumental and laboratory methods. RESULTS: After 4 weeks of treatment with AM target BP level (.

Intermolecular interaction of fosinopril with bovine serum albumin (BSA): The multi-spectroscopic and computational investigation.

The intermolecular interaction of fosinopril, an angiotensin converting enzyme inhibitor with bovine serum albumin (BSA), has been investigated in physiological buffer (pH 7.4) by multi-spectroscopic methods and molecular docking technique. The results obtained from fluorescence and UV absorption spectroscopy revealed that the fluorescence quenching mechanism of BSA induced by fosinopril was mediated by the combined dynamic and static quenching, and the static quenching was dominant in this system. The binding constant, Kb , value was found to lie between 2.69 × 103 and 9.55 × 103  M-1 at experimental temperatures (293, 298, 303, and 308 K), implying the low or intermediate binding affinity between fosinopril and BSA. Competitive binding experiments with site markers (phenylbutazone and diazepam) suggested that fosinopril preferentially bound to the site I in sub-domain IIA on BSA, as evidenced by molecular docking analysis. The negative sign for enthalpy change (ΔH0 ) and entropy change (ΔS0 ) indicated that van der Waals force and hydrogen bonds played important roles in the fosinopril-BSA interaction, and 8-anilino-1-naphthalenesulfonate binding assay experiments offered evidence of the involvements of hydrophobic interactions. Moreover, spectroscopic results (synchronous fluorescence, 3-dimensional fluorescence, and Fourier transform infrared spectroscopy) indicated a slight conformational change in BSA upon fosinopril interaction.

Improvement Effects of 3 Kinds of Angiotensin Converting Enzyme Inhibitor on Ventricular Remodeling in Patients with Acute Myocardial Infarction / 中国药房

OBJECTIVE: To observe the improvement effects of angiotensin converting enzyme inhibitor (ACEI) fosinopril, perindopril and benazepril on ventricular remodeling in patients with acute myocardial infarction (AMI), and to evaluate its safety. METHODS: A total of 96 AMI patients selected from our hospital during Jan. 2014-Oct. 2016 were divided into group A, B, C according to random number table, with 32 cases in each group. All patients received symptomatic treatment, underwent percutaneous coronary intervention, and then given ACEI after blood vessels recanalization and keeping blood pressure stable. Group A was given Fosinopril sodium tablets 10 mg, qd; group B was given Perindopril tert-butylamine tablets 4 mg, qd; group C was given Benazepril hydrochloride tablets 10 mg, qd. All groups were treated for consecutive 6 months. Cardiac structure and function indexes (LVESD, LVEDD, IVSD, LVPWD, LVEF, CO), hemodynamic indexes (SBP, DBP, HR) and related lab indexes (FPG, TG, TC, HDL-C, LDL-C, AST, ALT, Scr, BUN) of 3 groups were observed before and after treatment. The occurrence of ADR was recorded. RESULTS: Before treatment, there was no statistical significance in cardiac structure and function indexes, hemodynamic indexes or related lab indexes among 3 groups (P＞0. 05). After treatment, the levels of LVESD, LVEDD, LVPWD, CO, HR, FPG, TG, TC and LDL-C in 3 groups were decreased significantly, while the levels of LVEF and SBP were increased significantly, with statistical significance (尸＜0. 05). There was no statistical significance in above indexes among 3 groups after treatment (P＞0. 05). After treatment, the level of Scr in group B was significantly increased and higher than group A and C, with statistical significance (P＜0. 05). There was no statistical significance in the levels of IVSD, DBP, HDL-C, AST, ALT or BUN among 3 groups before and after treatment as well as the level of Scr between group A and C (P＞ 0. 05). There was no statistical significance in the incidence of ADR among 3 groups(P＞0. 05). CONCLUSIONS: Fosinopril, perindopril and benazepril can significantly improve ventricular remodeling in AMI patients, narrowing the heart cavity, increasing systolic pressure, lowering heart rate, reducing the oxygen consumption of the ventricle, with similar effects. Perindopril may increase the level of Scr, so fosinopril and benazepril are safe and suitable for AMI patients with renal function disorder.

Pharmacoeconomic evaluation on three different anti-hypertensive treatments / 药学实践杂志

Objective To compare three different anti-hypertension therapeutic projects by pharmacoeconomic evaluation and to find out the best therapeutic project.Methods Retrospective study was used.120 patients with hypertension were ran-domly assigned to group A(fosinopril sodium),group B(valsartan),group C(amlodipine besylate tablet),the therapeutic effects were observed and were evaluated by cost minimization analysis.Results The total efficiency of A,B,C group were 90·7%, 92·3%,92.1%(P>0.05)respectively.The incidence of adverse reaction were 16.7%,7.7%,13.2%(P>0.05)respective-ly.The costs were 287.3 yuan,378.7 yuan and 320.4 yuan respectively.Conclution The effectiveness of the three groups was similar.In terms of pharmacoeconomics,group A was the best therapeutic project.