Fosinopril Research Articles

Short-term effect of fosinopril on left ventricular hypertrophy and diastolic function in patients with essential hypertension

to assess the effect of angiotensin-converting enzyme inhibitor fosinopril (FOS) on left ventricular (LV) diastolic function and LV mass in essential hypertension (EH) patients. 22 patients with EH (aged 44±9years) were treated 10 or 20 mg FOS daily for 8 weeks. The patients were examined by M-mode and Doppler echocardiography. LV mass index (LVMI), intraventicular septal thickness and posterior wall thickness in diastole, relative wall thickness (RWT), ejection fraction (EF), early filling velocity (E), late filling velocity (A), E/A ratio, time velocity integral of early filling (VTI E), time velocity integral of late filling, isovolumic relaxation time (IVRT), deceleration time were determined. Blood pressure (BP) was measured by 24-hour ambulatory monitoring. FOS 8-week treatment resulted in a significant fall of average 24-hour BP, average daytime BP, average nighttime BP. LVMI decreased from 129,9±10,5 to 113,9±7,5 g/m2 (p<0,05), RWT - from 0,40±0,01 to 0,36±0,01 (p<0,05). This reduction was associated with significant decreases in LV septal wall thickness (from 1,15±0,07 to 1,05±0,04 cm, p<0,05) without negative changes in LV systolic function (EF increased from 61,0±2,0 to 67,9±1,5 %, p<0,05). It was founded a modest relationship between reductions in BP and a decrease in LVMI. During treatment LV diastolic filling and relaxation were improved in EH patients with E/A<1: E (from 0,61±0,05 to 0,67±0,06 m/s, p<0,05), VTI E (from 0,087±0,01 to 0,099±0,01 m, p<0,05), E/A (from 0,92±0,1 to 1,05±0,1, p<0,05) and IVRT (from 100,0±4,2 to 94,2±3,9 ms, p<0,05). In spite of short period of treatment, FOS influence on LV mass and diastolic function in EH patients. These findings support the concept that nonhemodynamic mechanisms also participate in short-term therapeutic changes.

Enhanced antihypertensive responses to Omapatrilat (OMA) relative to Fosinopril (FOS) in stroke-prone spontaneously rats (SHRSP) are independent of effects on renal sodium excretion

Enhanced antihypertensive responses to Omapatrilat (OMA) relative to Fosinopril (FOS) in stroke-prone spontaneously rats (SHRSP) are independent of effects on renal sodium excretion

RAPID AND ACCURATE SIMULTANEOUS DETERMINATION OF FOSINOPRIL SODIUM AND HYDROCHLOROTHIAZIDE IN TABLETS BY HPLC

A new, simple, precise, accurate, and rapid reverse-phase high performance liquid chromatographic (RP-HPLC) method has been developed for the simultaneous determination of fosinopril sodium and hydrochlorothiazide from tablets. The procedure is based on the use of the RP-HPLC method with a UV detector. Each analysis requires no longer than 6 minutes. A reversed phase C18 column with a mobile phase composed of a mixture of methanol: water (40:60, v/v), adjusted to pH 4 with 10% orthophosphoric acid, was used to separate both compounds with sulfamethoxazole, as an internal standard, in a reasonable time period. The linearity range for fosinopril sodium and hydrochlorothiazide was 1.6–30 μg/mL and 1–30 μg/mL, respectively. The detection limits for fosinopril sodium and hydrochlorothiazide were 0.29 μg/mL and 0.26 μg/mL, respectively.

A liquid chromatographic lon-pairing method for simultaneous determination of benazepril hydrochloride, fosinopril sodium, ramipril and hydrochlorothiazide in pharmaceutical formulations

A rapid and accurate reversed-phase ion-pairing liquid chromatographic method with UV detection was developed for the simultaneous assay of the angiotensin-converting enzyme inhibitors benazepril hydrochloride, fosinopril sodium and ramipril, and the diuretic hydrochorothiazide.

A New Treatment forInterdialytic Hyperkalemia – The Use of Fosinopril Sodium

Fosinopril sodium is the first of the phosphinic acid class of angiotensin-converting enzyme inhibitors (ACEI). It is used as an antihypertensive agent, but differs from other ACEI in its dual routes of excretion (liver and kidney), and less incidence of hyperkalemia and cough. We conducted a study in known chronic hemodialysis patients who developed interdialytic hyperkalemia in spite of other treatments to control hyperkalemia. We used fosinopril in this group of patients to assess the effect of fosinopril on serum potassium (K) levels. Twenty-four patients were given fosinopril 10 mg at 18:00 h daily for 8 weeks. K levels were measured before and after each dialysis treatment. Interdialytic weight gains were recorded. The average pretrial potassium level was 6.57 mmol/l (± 0.47), and the posttrial level was 5.34 (± 0.76); p ≤ 0.0001. No statistically significant interdialytic weight gain or reduction occurred. No first dose hypertensive effect or cough were reported. We have found the use of fosinopril to be successful in lowering predialysis serum K levels in hyperkalemic dialysis patients.

Clinical Trial of Fosinopril Sodium in Hypertensive Patients with Renal Insufficiency

Clinical Trial of Fosinopril Sodium in Hypertensive Patients with Renal Insufficiency

Fosinopril in the elderly ???

Fosinopril in the elderly ???

Generation and Fate of Regioisomeric Side-Chain Impurities in the Preparation of Fosinopril Sodium

A regioisomeric impurity is routinely formed during preparation of the first intermediate of the fosinopril sodium side chain. This first step, the radical-initiated condensation of 4-phenyl-1-butene (1) and aqueous hypophosphorous acid, provides low levels of the phosphinic acid (8) resulting from carbon−phosphorus bond formation to the internal olefin carbon. This impurity was isolated by preparative chromatography, and its structure was proven by independent synthesis. Subsequent reactions of 8 in the two following steps produce the corresponding regioisomeric impurities. Pure samples of these impurities were prepared for HPLC analysis to determine potential impact on the quality of intermediates downstream. The initial regioisomer averages 2 area % in manufacturing batches, and the levels of regioisomeric impurities diminish sharply with sequential conversion to further side-chain intermediates. After two steps, the levels of the regioisomeric impurities have been less than 0.08 area % in production b...

Fosinopril reduces incipient glomerulosclerosis induced by cholesterol

Fosinopril reduces incipient glomerulosclerosis induced by cholesterol

Determination of fosinopril in pharmaceutical formulations containing hydrochlorothiazide by multiwavelength UV spectrophotometry

A sensitive, simple, rapid and precise method for the simultaneous determination of fosinopril (FOS) and hydrochlorothiazide (HCT) in pharmaceutical formulations is presented. These active ingredients are extracted in aqueous solution and measured by multiwavelength UV spectrophotometry using the program QUEST. HCT acts as an internal standard to verify the accuracy of the analysis. Some aspects of the chemical, spectroscopic and thermoanalytical behaviour of FOS are also reported.

The determination of palladium in fosinopril sodium (monopril) by ICP-MS

A rapid, sensitive ICP-MS method was developed to determine palladium in fosinopril sodium. The assay could not be carried out in a purely aqueous solvent owing to the instability of the palladium species in this media. It was found that the most appropriate vehcile for solubilization of this material was a solution of 25% (v/v) 2-butoxyethanol and water. A minimum quantifiable limit of 0.1 μm g −1 for Pd in the sample (corresponding to 1 ng Pd mL −1 in the analyte solution) was obtained.

Aggregation Behavior of Fosinopril Sodium - A New Angiotensin-Converting Enzyme Inhibitor

Fosinopril sodium is an effective new angiotensin‐converting enzyme (ACE) inhibitor that is very useful for the clinical treatment of hypertension. After oral administration, fosinopril sodium is only partially absorbed (about one third of the drug). We studied the solution behavior of fosinopril sodium in aqueous media by a combination of high‐resolution nuclear magnetic resonance (NMR) spectroscopy and laser light scattering (LLS). LLS characterizes the self‐association properties of fosinopril sodium in solution, and NMR chemical shifts provide information on molecular conformation and interactions. The results revealed that fosinopril sodium has a micelle‐like self‐association behavior with a critical micelle concentration (cmc) ∼1.5 mg/mL. Hydrophobic interactions could induce formation of micellar aggregates, which had a narrow hydrodynamic size distribution, with an average diameter of ∼150 nm at concentrations above the cmc. The surface activity and self‐association of fosinopril sodium may be responsible for its early observed concentration‐dependent stability in aqueous solution, unexpected decrease in solubility in the presence of metal ions, as well as the limited absorption in clinical studies.

Quantitative analysis of fosinopril sodium by capillary zone electrophoresis and liquid chromatography

A capillary zone electrophoresis (CZE) method was developed for the quantitative analysis of fosinopril sodium. Validation parameters of the CZE method were evaluated and compared to an existing LC method. In terms of precision and sensitivity, LC performance was superior to that of the CZE method for this application. The CZE method achieved better selectivity for several degradants of interest within a much shorter analysis time than did the LC method. Effects of detection wavelength, applied voltage and buffer concentration on optimization of the CZE method are presented. Effects of diluent composition on capillary loading and peak behaviour are also discussed.

The Use of Zofenopril and Fosinopril in Acute Myocardial Infarction and Carotid Artery Disease

The potential of angiotensin-converting enzyme (ACE) inhibitors to protect the heart is a topic that has emerged recently as matter of scientific discussion. Experimental and clinical studies have shown the beneficial effects of ACE inhibitors on the metabolism, function, and structure of healthy and damaged hearts and these studies support the concept of both primary and secondary "cardioprotection" with these drugs. More recently, the prevention of atherosclerotic lesions has been demonstrated in animal models, extending the concept to a more general definition of "cardiovascular" protection with ACE inhibitors involving both the heart and the vessels. The potential role of ACE inhibitors on the primary prevention of atherosclerotic disease in humans is currently evaluated in PHYLLIS (Plaque HYpertension Lipid Lowering Italian Study), a multicenter clinical trial in which fosinopril sodium, a new ACE inhibitor, is administered to hypertensive patients with at least one uncomplicated carotid artery lesion. The primary aim of the study is to evaluate the effect of the drug on the long-term (3 years) progression of carotid artery atherosclerosis, noninvasively detected by B-mode ultrasound imaging. In addition to studies on primary prevention, some large clinical trials have been conducted to establish the role of ACE inhibitors on secondary prevention, in particular in patients with acute myocardial infarction (MI). The beneficial effect of these drugs is well established when administered in the subacute phase of acute MI.(ABSTRACT TRUNCATED AT 250 WORDS)

A Lamellar Liquid Crystal with Fosinopril Sodium

The location and conformation of fosinopril sodium (FS) in a lamellar liquid crystal of water, sodium dodecyl sulfate, and decanol was studied by low‐angle X‐ray diffraction. The result showed the FS molecule to be located within the amphiphilic part of the liquid crystalline structure with the polar parts anchored at the water/polar part interface. An area per molecule in the range of 95–100 Å2 showed not only the polar groups but also the benzene ring to be located at this interface.

Switching to fosinopril improves cough

Switching to fosinopril improves cough

Metabolic effects of converting enzyme inhibitors: Focus on the reduction of cholesterol and lipoprotein(a) by fosinopril

It is generally believed that the use of angiotensin-converting enzyme (ACE) inhibitors has no effect on the lipid profile. Our recent data show that in patients with proteinuric renal disease, serum levels of total cholesterol and lipoprotein(a) [Lp(a)] may be lowered during treatment with an ACE inhibitor, fosinopril sodium. During a 12-week randomized, placebo-controlled, double-blind study involving 26 patients with mild-to-moderate renal impairment, fosinopril administration was associated with significant decreases in both urinary protein excretion and serum total cholesterol levels, whereas placebo was not. During a 6-week washout phase, both parameters returned to baseline in fosinopril-treated patients and remained unchanged in placebo recipients. In addition, fosinopril-treated patients had a decrease in plasma levels of Lp(a), whereas this was not seen in placebo-treated patients. When data from a subset of 13 patients with proteinuric renal disease and hypertension were examined, a significant decrease in serum total cholesterol levels was observed; this decrease reversed after discontinuation of fosinopril. Analysis of the effect of fosinopril on plasma Lp(a) levels in a subset of patients who had type II diabetes mellitus and overt proteinuria revealed a significant decrease in plasma Lp(a) after administration of fosinopril. Moreover, fosinopril lowered plasma Lp(a) levels in blacks, whose pretreatment levels were higher than those of whites with comparable degrees of proteinuria and levels of serum total cholesterol. Thus, the reduction in serum Lp(a) levels may be related not only to amelioration of proteinuria, but also to another direct action of fosinopril on the metabolism of Lp(a).

Improvement of Lipid Abnormalities Associated with Proteinuria Using Fosinopril, an Angiotensin-Converting Enzyme Inhibitor

To examine whether reducing protein excretion in patients with proteinuric renal disease using an angiotensin-converting enzyme inhibitor, fosinopril sodium, would be accompanied by an amelioration of the associated hyperlipidemia. A randomized, placebo-controlled, double-blind study of 12 weeks, followed by 23 weeks of an open-label trial using fosinopril. Outpatient renal clinics. Twenty-six patients (age range, 28 to 70 years) with mild to moderate renal impairment and proteinuria associated with type II diabetes (15 patients) and other causes of nondiabetic renal disease (11 patients) completed the double-blind phase of the study. All patients except one were men. Fosinopril, 10 mg initial oral daily dose (randomized trial), and 20 mg orally once a day (open-label phase). Proteinuria and serum lipids (total cholesterol, high-density lipoprotein, and low-density lipoprotein [LDL] cholesterol, and lipoprotein(a) protein). In a group of 17 patients treated with fosinopril, protein excretion decreased from 5.56 to 4.28 g/d, a reduction of 1.28 (95% CI, -2.49 to -0.08). The reduction was associated with a decrease in serum total cholesterol from 6.39 to 5.82 mmol/L, a decrease of 0.58 mmol/L (CI, -1.01 to -0.15 mmol/L). In a group of nine patients treated with placebo, neither protein excretion (from 5.11 to 4.81 g/d, a change of -0.29 g/d [CI, -1.78 to +1.13 g/d]) nor serum total cholesterol (from 6.08 to 5.77 mmol/L, a change of -0.31 mmol/L [CI, -0.78 to +0.13 mmol/L]) change significantly. At the end of the double-blind phase, plasma lipoprotein(a) protein decreased in the fosinopril-treated group (from 3.94 to 3.33 mg/dL, a reduction of 0.60 mg/dL [CI, -1.02 to -0.18 mg/dL]) but not in the placebo group (from 2.85 to 3.19 mg/dL, a change of +0.34 mg/dL [CI, -0.53 to +1.2 mg/dL]). Dietary protein and fat intake were similar in the two groups throughout the study. In 16 patients who completed an extended open-label phase, fosinopril was associted with a decrease in protein excretion from 4.53 to 3.22 g/d, a reduction of 1.29 g/d (CI, -2.54 to -0.05 g/d), which was associated with a reduction in serum total cholesterol (from 6.37 to 5.54 mmol/L, a decrease of 0.84 mmol/L [CI, -1.59 to -0.08 mmol/L]), LDL cholesterol (from 4.38 to 3.72 mmol/L [a decrease of 0.68 mmol/L [CI, -1.33 to -0.03 mmol/L]), and plasma lipoprotein(a) protein (from 3.58 to 2.81 mg/dL, a reduction of 0.82 mg/dL [CI, -1.58 to -0.05 mg/dL]). The angiotensin-converting enzyme inhibitor, fosinopril, can result in a sustained reduction in serum total cholesterol, LDL cholesterol, and plasma lipoprotein(a) protein levels in conjunction with a partial reduction in proteinuria.

Mechanism and kinetics of metal ion-mediated degradation of fosinopril sodium.

Fosinopril sodium (I), a new angiotensin converting enzyme inhibitor, is a diester prodrug of the active moiety II. We report here a novel transformation of fosinopril into beta-ketoamide, III, and a phosphonic acid, IV, mediated through metal ion participation. The interaction of fosinopril with magnesium ions was studied in a solution model system in which methanol was used as the solvent and magnesium acetate as the source of metal ions. Kinetic analysis indicated the degradation to be a bimolecular process, with the rate being first order in both metal ion and fosinopril concentration. The degradation products II, III, and IV effectively retarded the magnesium ion mediated reaction of fosinopril. Based on the results of 31P-NMR, 1H-NMR, Mn(II)-EPR spectroscopy experiments and mass spectrometry, a mechanism is postulated for this transformation. A key reactive intermediate has been characterized that supports the proposed mechanism. The results can account for the observed degradation profile of the fosinopril sodium in a prototype tablet formulation.

Solid-state NMR and IR for the analysis of pharmaceutical solids: Polymorphs of fosinopril sodium

The two polymorphic modifications of fosinopril sodium have been characterized as to their differences in melting behaviour, powder X-ray diffraction patterns, Fourier transform infrared spectra (FTIR), and solid-state 31P- and 13C-NMR spectra. The polymorphs were found to be enantiotropically related based upon melting point, heat of fusion, and solution mediated transformation data. Analysis of the solid-state FTIR and 13C-NMR data indicated that the environment of the acetal side chain of fosinopril sodium differed in two polymorphs, and that there might be cis-trans isomerization about the C 6—N peptide bond. These conformational differences are postulated as the origin of the observed polymorphism.