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At least 19 recordsLinked to original sources
PubMed1984

High-performance liquid chromatographic determination of the nitrate esters isosorbide dinitrate, pentaerythritol tetranitrate, and erythrityl tetranitrate in various tablet forms.

A reliable, sensitive, and specific assay for isosorbide dinitrate pentaerythritol tetranitrate, and erythrityl tetranitrate in sublingual, uncoated, sustained-release, and chewable dosage forms, using high-performance liquid chromatography, is described. The nitrate ester dosage forms were dissolved in methanol, filtered, and injected directly into the liquid chromatograph. A variable-wavelength UV detector, operated at 220 nm, and a reverse-phase C18 microporous silica column were employed. The mobile phase was methanol-water (40:60). The proposed method is quantitative and reproducible.

Chromatography, High Pressure Liquid↗
PubMed1982

[Treatment of chronic congestive failure with vasodilators (acute trial with prazosin and erythrityl tetranitrate)].

An acute clinical experiment was carried out with 34 patients with chronic refractory cardiac insufficiency with stasis and idiopathic dilating (stasis) cardiomyopathy so as to follow up the hemodynamic effect of the vasodilators prazosin and erythrityl tetranitrate. The values of the central and peripheral vascular hemodynamics were followed up before and one hour after the peroral intake of 2 mg prazosin and half an hour after the peroral intake of 40 mg erythrityl tetranitrate. The results indicate that a statistically significant decrease of the arterial pressure and the total peripheral vascular resistance developed after prazosin intake. The systolic arterial pressure was decreased from 121,80 +/- 3,52 to 102,40 +/- 3,71 (p less than 0,001) and the diastolic--from 80,20 +/- 2,41 to 68,20 +/- 2,56 (p less than 0,01). The values of the total peripheral vascular resistance were decreased from 2629,65 +/- 174 to 1865,53 +/- 153 (p less than 0,001). The indices of the pump function--Stl and SI were increased (Stl from 22,74 +/- 1,85 to 30,37 +/- 2,14 with p less than 0,025 and Sl--from 1,90 +/- 0,08 to 2,64 +/- 0,19; p less than 0,02). The indices of the pressure in the left ventricular filling had no statistically significant change. After the administration of erythrityl tetranitrate, a statistically significant improvement of the indices of the cardiac output was also observed as well as of the total peripheral vascular resistance. The systolic index grew from 1,74 +/- 0,20 to 2,70 +/- 0,16 (p less than 0,01); stroke index--from 18,35 +/- 2,82 to 32,99 +/- 2,88 (p less than 0,01), and the total peripheral vascular resistance was decreased from 2897,0 +/- 186,0 to 1556,0 +/- 154,0 (p less than 0,001). Prazosin and erythrityl tetranitrate led to a considerable decrease of the counter load of the heart and improvement of the pump function of left ventricle in an acute experiment in case of chronic cardiac insufficiency with stasis.

Adult↗
PubMed1981

Digital plethysmography for assessing erythrityl tetranitrate bioavailability.

The bioavailability or oral, sublingual, and chewable tablets or erythrityl tetranitrate (ETN) was evaluated in 15 normal men. In a randomized, complete crossover investigation with nitroglycerin and placebo controls, drug-induced changes in the diastolic amplitude response intensity were measured with a digital plethysmogram. Values for area under the response intensity curve (AUC), maximum response intensity (Imax), and time lapse from dosing to peak response (tmax) were obtained by computer processing and converted to intensity values and AUC segments for specific time intervals. Sublingual nitroglycerin induced a response (p less than 0.05) from placebo within the first hour. Although somewhat slower in reaching peak intensity, all forms of ETN induced significant responses over placebo (p less than 0.05) for 2 hr, with oral (swallowed) ETN different 6 hr. Our results indicate that all the ETN dosage forms were bioavailable, with the longest duration of effect by the oral form.

Administration, Oral↗
PubMed1981

[Vasodilator treatment of chronic heart failure: a chronic double-blind trial with prazosin and erythrityl tetranitrate].

A chronic double-blind experiment was carried out with 32 patients with severe chronic stasis cardiac insufficiency, with concomitant idiopathic congestive cardiomyopathy and ischemic heart disease, in assessing the effect of vasodilators prazosin or erythrityl tetranitrate upon the decompensation symptomatics and hemodynamic indices. The clinical indices of cardiac insufficiency with hemodynamic signs of pre-loading, myocardial contractility and postloading of left ventricle were followed up. Besides vasodilators the patients were administered the ordinary maintenance therapy with digoxin and diuretics. The experiment was a double blind one, controlled by placebo-periods and covered a 6 months follow-up period. The combined venous-arteriolar vasodilator prazosin was reduced pre and post-loading, it increased the cardiac output, without essential changes in functional capacity of the patients with chronic cardiac insufficiency. Erythrityl tetranitrate, however, has no substantial effect on the clinical and hemodynamic indices of statis cardiac insufficiency even in higher doses. That suggests the necessity of the chronic cardiac insufficiency treatment to be carried out with vasodilators with venous and arteriolar effect.

Chronic Disease↗
PubMedDate not supplied

Erythrityl tetranitrate compared with isosorbide dinitrate. Effects on systolic time intervals and nitrate modification of effects of food.

The pharmacologic effects of erythrityl tetranitrate (ETN) and isosorbide dinitrate (ISDN) were compared to placebo using systolic time intervals (STI) in a randomized, double-blind study in 15 fasted male volunteers. Sublingual doses of ETN 5 mg, ISDN 5 mg, and placebo were administered to each volunteer at weekly intervals, and measurements of heart rate and STI [pre-ejection period (PEP), left ventricular ejection time (LVET), and PEP/LVET ratio] were made serially for up to 6 hours after each dose. STI were determined using ear densitography. Evaluation of the pharmacologic effects of ETN and ISDN were based on placebo-corrected changes from baseline values. Ejection time index (ETI) [LVET corrected for heart rate] was shortened, but the changes were not statistically significant for either drug. However, after ETN and ISDN, statistically significant (p less than 0.05) changes in PEP and PEP/LVET ratio were demonstrated for up to 240 minutes after dosing. Unexpected marked changes in the baseline corrected PEP/LVET ratio were observed following food at 4 hours after dosing. This suggests increased inotropy during the postprandial period.

Adult↗
PubMed1998

Erythrityl tetranitrate; drug efficacy study implementation; revocation of exemption; opportunity for a hearing--FDA. Notice.

The Food and Drug Administration (FDA) is revoking the temporary exemption that has allowed single-entity coronary vasodilator drug products containing erythrityl tetranitrate to remain on the market beyond the time limits scheduled for implementation of the Drug Efficacy Study. FDA is announcing that the products lack substantial evidence of effectiveness and is offering an opportunity for a hearing on a proposal to withdraw approval of any applicable new drug applications (NDA's) or abbreviated new drug applications (ANDA's).

Drug Approval↗
PubMedDate not supplied

Erythrityl tetranitrate: sustained effects on systolic time intervals. changes consistent with sustained preload reduction.

The effects of sustained preload reduction have been demonstrated for several nitrates but not for erythrityl titranitrate. In seven patients with coronary heart disease, a randomized double-blind crossover clinical trial showed that chewable erthrityl tetranitrate, 10 mg, produced significant changes in systolic time intervals consistent with preload reduction and lasting for at least four hours. As compared with placebo, ejection time index (ETI) fell and remained significantly low between 6 and 90 minutes after administration, and pre-ejection period (PEP), isovolumic contraction time IVCT), and pre-ejection period/left ventricular ejection time (PEP/LVET) rose and remained significantly increased between 22 minutes and the four-hour endpoint. We conclude that erythrityl tetranitrate is a physiologically effective long-acting agents in patients with coronary heart disease.

Clinical Trials as Topic↗
PubMedDate not supplied

Bioavailability of organic nitrates: a comparison of methods for evaluating plethysmographic responses.

Erythrityl tetranitrate, a long-acting organic nitrate, was compared with isosorbide dinitrate in a double-blind, placebo-controlled complete crossover study in 15 healthy male volunteers. A digital plethysmogram and ear densitogram were used to assess the physiologic response to these two sublingual nitrates, with the intensity and duration of drug effect calculated by differences in diastolic amplitude intensity before and after drug administration. Both 5 mg sublingual erythrityl tetranitrate and 5 mg isosorbide dinitrate produced significant increases in diastolic amplitude intensity for up to 3 hours. The erythrityl tetranitrate peak effect was less than that of the isosorbide dinitrate, but the incidence of headaches was also less. The ear densitogram was found to be an effective means of assessing the diastolic amplitude intensity changes.

Adult↗
PubMed1999

Nitric oxide modulation of the growth hormone-releasing activity of Hexarelin in young and old dogs.

The growth hormone (GH)-releasing activity of Hexarelin, a potent GH-releasing peptide (GHRP) analog, was evaluated in eight young (aged 1 to 6 years) and five old (10 to 16 years) beagle dogs pretreated with erythrityl tetranitrate, a liposoluble nitric oxide (NO) donor, and/or indomethacin, an inhibitor of cyclooxygenase enzymes, and N-nitro-L- or N-nitro-D-arginine methylester (L-NAME and D-NAME), active and inactive NO synthase (NOS) inhibitors, respectively. Erythrityl tetranitrate (0.3 mg x kg(-1) oral [p.o.]) strikingly potentiated Hexarelin-stimulated GH secretion (31.25 microg x kg(-1) intravenous [i.v.]) in both young (area under the time-concentration curve at 0 to 90 minutes AUC(0-90)] 878.50 +/- 267.02 v 1,994.04 +/- 434.20 ng x mL(-1) x h, P < .01) and aged animals (314.82 +/- 117.11 v 1,314.12 +/- 484.75 ng x mL(-1) x h, P < .01). The NO donor alone did not modify baseline GH levels in either young dogs (188.68 +/- 85.24 ng x mL(-1) x h) or old dogs (120.49 +/- 22.03 ng x mL(-1) x h). L-NAME (5 mg x kg(-1) x 2 i.v.) suppressed GH release induced by the peptide in young dogs (1,367.68 +/- 251.87 v 411.12 +/- 68.49 ng x mL(-1) x h, P < .01), but potentiated it in old dogs (314.73 +/- 117.10 v 1,103.97 +/- 374.11 ng x mL(-1) x h, P < .01). D-NAME (5 mg x kg(-1) x 2 i.v.) did not affect the GH response to Hexarelin in either young (1,328.68 +/- 433.54 ng x mL(-1) x h) or aged (342.32 +/- 84.82 ng x mL(-1) x h) dogs. Indomethacin (1.5 mg x kg(-1) i.m.) abolished the NO-donor potentiation of the GH response induced by Hexarelin in both young dogs (1,627.25 +/- 260.90 v 1,163.37 +/- 334.84 ng x mL(-1) x h, P < .05) and old dogs (1,061.47 +/- 210.38 v 365.69 +/- 79.27 ng x mL(-1) x h, P < .01) without affecting the plasma GH peak evoked by the peptide alone (young dogs, 786.04 +/- 153.44 v 960.04 +/- 444.44 ng x mL(-1) x h, P = NS; old dogs, 474.55 +/- 47.30 v 490.82 +/- 144.86 ng x mL(-1) x h, P = NS). In conclusion, (1) NO donors are capable to further increase the strong GH-releasing activity of Hexarelin in both young and old dogs, although the site(s) and mechanism(s) of action of NO is still obscure; (2) the different GH response to the peptide after NOS inhibition in young and old dogs signifies in the latter an alteration of the somatotrope function; and (3) prostaglandins are the downstream effectors of the chain of events triggered by activation of the NO-ergic system.

Aging↗
PubMed1970

Effect of organic nitrates on myocardial oxygen consumption in vitro.

1. Mannitol hexanitrate (MANHN), iditol hexanitrate and sorbitan tetranitrate, all at 442 muM, stimulate oxygen uptake by isolated rabbit atrial tissue.2. At the same concentration, glyceryl trinitrate decreased oxygen uptake, while isosorbide dinitrate and erythrityl tetranitrate had no effect.3. No simple correlation was found between the lipoid solubility or per cent nitration of these compounds and their effects on oxygen uptake.4. The stimulating effect of MANHN and its possible role as an uncoupler of oxidative phosphorylation is discussed.

Animals↗
PubMed1982

[Clinical and statistical study of 121 cases of acute myocardial infarct from 1976 to 1981 (month of April). Critical review].

The authors realized a retrospective clinical-statistical study about 121 cases of acute myocardial infarction (AMI), treated in the Department of general medicine with a pharmacological association of Lysine acetylsalicylate--Erythrityl tetranitrate--Papaverine hydrochloride, with the purpose of obtaining a vasodilatation on coronary arteries and a platelet antiaggregation, in the light of the new etiopathogenetic views about the prolonged coronary spasm and the platelet aggregation, in some cases of myocardial infarction with or without thrombosis. Obtained data are very optimistic about incidence of left ventricular insufficiency and (of) thromboembolisms, to they augur the sistematic adoption of this treatment of AMI, especially as to the early antiaggregation therapy.

Adult↗
PubMed1975

Comparative vasodilator effects of nitroglycerin, pentaerythritol trinitrate and biometabolites, and other organic nitrates.

Previous studies in man have shown pentaerythritol (PE) trinitrate, given either sublingually or orally, produces a prolonged hypotensive effect. The coronary vasodilator and systemic vasodepressor activities of PE trinitrate and its metabolites, PE dinitrate, PE mononitrate and PE, were evaluated in dogs to determine whether the metabolites were active and contributory. Coronary vasodilator activity was estimated with a flow transducer placed on the left anterior descending artery, and reduction of arterial pressure was determined directly via the femoral artery. Quantitative comparisons were made from dose-response curves established for nitroglycerin (ng), PE nitrates, and other common organic nitrates after intrajugular administration. Increase of coronary blood flow and reduction of arterial pressure were proportionally related, and the proportionality was the same for all drugs. Relative to NG, the potency of PE trinitrate was about 20 percent, erythrityl tetranitrate 12 percent, and isosorbide dinitrate 3.5 percent. The ratios of vasodilator activity of PE trinitrate and its metabolities were: PE trinitrate 100; PE dinitrate 1.5; PE mononitrate 0.5; and PE O. Tachyphylaxis was observed after close-order injections of NG or PE trinitrate. In addition, there was cross tolerance between NG and PE trinitrate and also between PE trinitrate and its less active metabolites.

Animals↗
PubMed1987

Structure-activity relationship of organic nitrates for activation of guanylate cyclase.

The effect of different organic nitrates on the activity of soluble guanylate cyclase prepared from rat liver was investigated. We found a close correlation between the number of nitrate ester groups and the potency of guanylate cyclase activation. For erythrityl tetranitrate (ETN, EC50 = 14.5 microM), glyceryl trinitrate (GTN, EC50 = 60 microM), isoidide dinitrate (IIDN, EC50 = 0.24 mM) and isosorbide-5-nitrate (IS-5-N, EC50 = 1 mM), we were able to set up an equation by which the EC50 could be calculated from the number of nitrate groups per molecule. Compared to these results, the effect of sterical factors and lipophilicity on organic nitrate-induced activation of guanylate cyclase was small. However, there were still significant differences in the EC50 values for the cyclic mononitrates. Isosorbide-2-nitrate (IS-2-N, EC50 = 0.75 mM) was found to be more potent than the stereoisomeric isosorbide-5-nitrate. Similarly, the cyclic dinitrates isomannide dinitrate (IMDN, EC50 = 0.20 mM), isoidide dinitrate and isosorbide dinitrate (ISDN, EC50 = 0.28 mM) exhibited small but significant differences in their guanylate cyclase stimulatory potency. Two lipophilic ester derivatives of isosorbide-5-nitrate showed a 2-fold potency difference for vasodilation but were equipotent for activation of guanylate cyclase (EC50 = 0.85 mM). Also, the increase in lipophilicity due to esterification of the free hydroxylic group had no major influence on guanylate cyclase activation by isosorbide-5-nitrate. These results demonstrate that in a cell-free system, the potency of organic nitrates for guanylate cyclase activation is mainly determined by the number of nitrate groups. Since organic nitrate-induced activation of guanylate cyclase may involve the formation of nitric oxide free radicals, it is conceivable that the differences in potency reflect a varying degree of nitric oxide release from each compound tested.

Animals↗