Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Isosorbide”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 523 records · Page 29Linked to original sources
PubMed1987

Pharmacokinetics of isosorbide mononitrate in a new sustained release oral form in comparison with a conventional formulation.

40 mg of isosorbide mononitrate (isosorbide-5-mononitrate, IS5MN) in conventional (Ismo 20) and sustained release formulations (Ismo Diffutab) were administered to 5 male healthy volunteers. The administration of the sustained release formulation was repeated for seven days in order to evaluate the possible occurrence of accumulation. Pharmacokinetic data showed that the sustained release formulation reached significantly lower and delayed mean peak plasma levels compared with the conventional formulation, respectively 452.8 +/- 67.8 ng/ml and 706.7 +/- 57.3 (mean +/- SE) (p less than 0.05). Peak times were 4.6 +/- 0.2 and 2.4 +/- 0.2 (p less than 0.005) h, respectively. A longer plasma half-life together with larger AUC for the sustained release formulation was also observed. The pharmacokinetic parameters of the sustained release formulation are consistent with a therapeutic usefulness and suggest further clinical evaluation.

Administration, Oral↗
PubMed1985

Isosorbide-5-mononitrate--effective monotherapy in chronic stable angina.

Isosorbide-5-mononitrate (ISMN) is not subject to first-pass metabolism and has more predictable blood concentrations than isosorbide dinitrate. In order to evaluate its efficacy as monotherapy in patients with chronic stable angina, 14 patients were studied. All had angiographically proven coronary artery disease and were limited by angina on a treadmill exercise test. After a 2-week placebo period ISMN was administered in a single-blind fashion with the dosage being titrated at 2-week intervals. The dosage increments were 20 mg once daily, 20 mg twice daily, 40 mg once daily and 40 mg twice daily. Patients were assessed subjectively by anginal attack rate and glyceryl trinitrate (GTN) consumption and objectively by treadmill exercise testing at 12 hours post dosage. ISMN increased the exercise ability significantly on all dosage regimes. However, a significant reduction in ST depression occurred only with the twice-daily regime. The increased exercise performance was associated with a significant decrease in anginal attack rate and GTN consumption from the 20 mg b.i.d. increment. ISMN is an effective antianginal agent with a more favourable profile in twice-daily dosage. Whilst no significant differences emerged between 20 mg and 40 mg twice daily, individual variation occurred, indicating a need for dosage flexibility.

Administration, Oral↗
PubMed1985

Pharmacokinetics and bioavailability of isosorbide-5-mononitrate in humans.

The relative bioavailability of isosorbide-5-mononitrate from two different formulations (MONOCLAIR, ISMO) was investigated in a double-blind randomized cross-over study in 8 healthy human subjects. After single orale doses of 40 mg the plasma concentration and the urinary excretion of isosorbide-5-mononitrate were measured over 24 hours. The comparison of the results obtained over the whole experimental period showed a significantly higher plasma concentration with a higher renal excretion after MONOCLAIR, the latter changes being insignificant as compared with those after ISMO, the reference drug. Thus the two formulations are judged to be at least equivalent with regard to their drug bioavailability.

Adult↗
PubMed1983

In vivo and in vitro studies to elucidate the hemodynamic differences of sodium nitroprusside, nitroglycerin, and two isosorbide nitrates.

In isolated renal veins of the rabbit, isosorbide dinitrate and isosorbide-5-mononitrate were seven to twenty times more potent as relaxants than in renal arteries which explains their predilection for the capacitance vascular bed in vivo. For sodium nitroprusside (SNP) and nitroglycerin (NTG), the sensitivity was slightly greater in veins at threshold concentrations (EC10), but similar in veins and arteries at higher concentrations (EC50). After 30 min of exposure, the relaxant effect to NTG faded partially in arteries, but not in veins, which may underlie its preference for the capacitance vessels in vivo. In anaesthetized rats, SNP and NTG were infused i.v. or into the femoral artery. The hypotensive response to NTG was the same by either route of infusion, whereas that to SNP was considerably lower on infusion into the femoral artery; a 34% inactivation of SNP on passage through the hind leg was calculated. The result decrease in venous over arterial blood levels of SNP at a somewhat greater sensitivity of veins than of arteries may account for the balanced effect of SNP on resistance and capacitance vessels in vivo.

Animals↗
PubMed1984

Effects of long-term molsidomine treatment versus isosorbide dinitrate and placebo on exercise tolerance in stable angina.

A single-blind study (n = 59) was performed to assess the effect of long-term (4 week) orally administered molsidomine (2 mg 4 X daily), isosorbide dinitrate (10 mg 4 X daily), and placebo on exercise tolerance performed on the bicycle ergometer by patients with stable angina on effort and with significant coronary artery disease. Isosorbide dinitrate had similar effects to placebo, both failed to modify the pressure-rate product, the sustained work load, and the ST segment depression, but slightly decreased, although not significantly, the incidence of angina. Although not affecting the pressure-rate product and the mean blood pressure, molsidomine decreased significantly the ST segment depression (p less than .05). In conclusion, by markedly reducing preload and because of its long-lasting effect (up to 6 h), the new vasodilator drug molsidomine plays a useful role in the long-term management of stable angina on effort.

Angina Pectoris↗
PubMed1984

[Isosorbide dinitrate ointment in the long-term treatment of intermittent claudication].

We evaluated the long-term therapy with Isosorbide Dinitrate Ointment (ISDN-O): 300 mg daily on the painful leg area in 20 male patients (pts) affected by Intermittent Claudication. The efficacy of the treatment was assessed on the basis of the subjective evaluation of pain threshold (daily diary) and objectively by repeated treadmill stress tests performed by each patient at a constant speed, selected according to the severity of symptoms, and by the evaluation of changes both of the distance walked without symptoms (DWS) and of the maximal distance reached (MDR). The maximal duration of the test was 15 minutes independently from the speed. The reproducibility of treadmill tests and the acute effect of isosorbide dinitrate ointment administration were preliminarly evaluated in 2 groups of 5 patients each. The distance walked without symptoms and maximal distance reached in two control stress tests performed in two successive days were: distance walked without symptoms 37 +/- 29 vs 36 +/- 22 m (NS) and maximal distance reached 97 +/- 40 vs 98 +/- 37 m (NS). During the control period and 1 hour after the drug administration distance walked without symptoms was 34 +/- 31 vs 43 +/- 50 m (NS) and maximal distance reached 89 +/- 53 vs 97 +/- 57, (NS) respectively. In a group of 5 patients the effect of one month administration of placebo was evaluated: distance walked without symptoms was m 68 +/- 29 and m 104 +/- 62 and maximal distance reached was m 156 +/- 103 and m 188 +/- 97 basally and after 1 month of placebo (NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1983

Transient myopia following isosorbide dinitrate.

A 38-year-old white woman consistently developed transient myopia following the administration of isosorbide dinitrate (Isordil). The myopia was associated with a decreased amplitude of accommodation, a reduction of the AC/A ratio and was eliminated by cycloplegia. Ciliary spasm secondary to the ingestion of this medication is proposed as a possible explanation for the transient myopia. To our knowledge, this case represents the first case of transient myopia following isosorbide dinitrate administration.

Accommodation, Ocular↗
PubMed1983

Improved diagnostic yield of radionuclide angiography by quantitative phase analysis during resting angina and following isosorbide dinitrate.

The reliability of quantitative phase analysis of radionuclide angiography in the detection of wall motion abnormalities has been investigated in 15 patients with angina at rest. All patients have been studied in the basal state, during spontaneous or ergonovine-induced ischemia and following isosorbide dinitrate acute i.v. administration in the resolution phase. Quantitative phase analysis provided a more sensitive index of impaired wall motion as compared to global ejection fraction changes. Isosorbide dinitrate rapidly and completely solved ischemic dyssynergies caused by coronary vasospasm.

Adult↗
PubMed1983

Management of acute heart failure following myocardial infarction: hemodynamic advantages of isosorbide dinitrate over frusemide.

The immediate hemodynamic effects of intravenous frusemide (1 mg/kg) and intravenous isosorbide dinitrate (50-200 micrograms/kg/h) were compared in a prospective, randomized, between-group study in 28 men with radiographic and hemodynamic evidence of left ventricular failure following acute myocardial infarction. The diuresis induced by frusemide reduced the left-heart filling pressure and cardiac output and transiently raised systemic blood pressure. In contrast, isosorbide dinitrate was accompanied by a reduction in systemic blood pressure and peripheral resistance, with the result that the cardiac output was not decreased despite a large fall in the pulmonary vascular and left-heart filling pressures. The results indicate that reduction of excessive preload by venodilatation may be hemodynamically superior to that induced by diuresis in terms of both reducing myocardial oxygen consumption and maintaining peripheral perfusion. The influence of these contrasting treatments on the prognosis of these high-risk patients warrants further study.

Adult↗
PubMed1984

Pharmacokinetic aspects of isosorbide-5-mononitrate in dogs.

The aim of this study was to determine pharmacokinetic data of isosorbide-5-mononitrate (IS-5-MN) in dogs and to correlate them with the hemodynamic effects of this drug. Beagle dogs (n = 7) were given 3 mg/kg of IS-5-MN, the main metabolite of isosorbide-dinitrate, by i.v. injection and oral administration. At defined times blood samples were withdrawn from the vena cava caudalis for assaying IS-5-MN. In the experiments with oral administration the decrease in systolic blood pressure was monitored as a measure of hemodynamic response. The pharmacokinetic parameters were calculated from the plasma concentrations on the basis of an open two-compartment model. The half-life for the distribution phase was about 6 min, for the elimination phase about 1.5 hr. The latter is about one-third of that obtained in man. From the comparison of the areas under the curve, a bioavailability of 71.5% was estimated. In a second series of investigation dogs were given five different doses of IS-5-MN orally (3.125-50 mg/dog). These experiments showed a rise in the peak plasma concentration and the area under the curve proportional to the dose, whereas the terminal half-life did not differ markedly. A close correlation has been found in both series of investigations between the log concentration and the decrease in blood pressure. The minimum plasma concentration for a hemodynamic effect was estimated to be 100 ng/ml.

Administration, Oral↗
PubMed1978

Hemodynamic effects of cutaneously administered isosorbide dinitrate ointment.

With a view to testing the hemodynamic effects of a 10% isosorbide dinitrate ointment, about 40 mg of the drug was applied to the skin of nine cardiologically healthy volunteers. The ensuing hemodynamic changes were followed up for six hours by means of noninvasive techniques including echocardiography. As early as 30 min after drug application, significant decreases in heart rate, cardiac output, systolic blood pressure and intracardiac diameters were recorded. Only systolic blood pressure had returned to initial values by the end of the observation period. Isosorbide dinitrate ointment diminished myocardial oxygen consumption for a duration beyond six hr, by reducing pressure and heart-rate work of the left ventricle.

Administration, Topical↗
PubMed1982

[Pharmacokinetics of isosorbide dinitrate administered by intravenous infusion to hypertensive patients (author's transl)].

The pharmacokinetics of intravenous isosorbide dinitrate was investigated in 11 patients with labile hypertension and with normal renal and hepatic functions. The mode of administration (constant rate infusion without loading dose) was chosen in order to minimize side-effects and to approximate clinical conditions. Isosorbide dinitrate levels were measured by electron-capture gas chromatography. The volume of distribution during steady state (Vd beta = 318 +/- 117 I) and the elimination half-life (t1/2 beta = 64.8 +/- 30.5 min) were similar to those found after perlingual and oral administration. Systemic clearance (Cls = 3.80 +/- 1.48 I/min) was high for a drug given intravenously, presumably because of active hepatic extraction, intensive pre-systemic degradation and very active extra-hepatic metabolism. These findings should be compared with the considerable inter-individual variations observed in theoretical plasma concentrations during steady state and with the presence of two pharmacokinetic models (one -- and two -- compartments) in the patients under study. Comparison of the results obtained by the intravenous route with previously published results after perlingual and oral administration indicates the following bioavailability ratios: perlingual/i.v. = 31%, oral/i.v. = 20%, and oral/perlingual = 63%.

Female↗
PubMed1982

[Coronary artery dilatation induced by isosorbide dinitrate injection (author's transl)].

Twenty-six patients were given 3 mg isosorbide dinitrate either by direct intra-coronary injection (17 patients) or by intravenous injection ( patients), 5 minutes after an injection of 0.4 mg methylergometrine. In all 26 patients isosorbide dinitrate dilated the coronary arteries to a diameter that was 26% greater than the smallest diameter observed with methylergometrine and 14.8% greater than the basal diameter. The response was highly significant at 30 seconds, maximal at 2 minutes and lasted more than 10 minutes. At the dosage level used in this study, there was no significant difference between the two groups of patients. However, a rapid fall in systemic arterial pressure was noted after peripheral intravenous injection.

Coronary Vessels↗
PubMed1982

[Isosorbide dinitrate in the treatment of threatening myocardial infarction (author's transl)].

Thirty patients with threatening myocardial infarction were treated with intravenous isosorbide trinitrate. Eight patients had increasingly severe angina, 6 had de novo crescendo angina, 3 had Prinzmetal angina and 13 had signs of impending extension of a previous infarct. In all cases the anginal attacks occurred spontaneously. The drug was administered in association with a beta-blocker or a calcium antagonist. The initial dosage was 33 mcg/min and dosage adjustments ranged from 16 to 130 mcg/min. the main duration of treatment was 3.6 days. Pain was controlled in all patients. Anginal attacks ceased completely and permanently in 24, but the remaining 6 became isosorbide dinitrate-dependent and could only be weaned by aortocoronary bypass. The effects on the drug on heart rate and blood pressure remained moderate and never interfered with dosage adjustments. Coronary artery angiography was performed without any trouble in 25 patients, 21 of whom underwent myocardial revascularization by venous grafts.

Adult↗
PubMed1982

[Chronic aortic and mitral valve regurgitation. Effects of isosorbide dinitrate on systolic function and passive elastic properties of the left ventricle (author's transl)].

A haemodynamic and cineangiographic study was conducted in 20 patients with chronic aortic regurgitation alone or associated with mitral regurgitation before and during i.v. administration of isosorbide dinitrate 5 mg/hour. Freedom from coronary disease had been ascertained. The heart rate and aortic pressure (initially normal), cardiac index (initially low), pulmonary pressures and pulmonary and systemic resistances (slightly raised initially) remained unchanged. On the other hand, the left ventricular (LV) filling pressure, distinctly raised before treatment, was reduced by 17% (p less than 0.05). There was also a 10% reduction in LV end-diastolic volume (from 204 +/- 60- cm3.m2 to 184 +/- 56 cm3,m2; p less than 0.001) and a 14% reduction in LV end-systolic volume (from 104 +/- 39 cm3.m2 to 89 +/- 40 cm3.m3; p less than 0.001). LV geometry, stroke volume and regurgitation volume were unmodified. There was a significant improvement in ventricular function indices, globally reduced before treatment: + 8% for the fiber shortening amplitude (p less than 0.025), + 6% for the ejection fraction (p fiber shortening (p less than 0.01), and + 15% for the ESP: ESV ratio (p less than 0.05). The passive elasticity indices, all increased before treatment, also improved. It is concluded that isosorbide dinitrate improves LV systolic and diastolic functions in patients with chronic valve disease.

Adolescent↗
PubMed1981

[Plethysmographic researches on the beginning and duration of the pharmacological action of an isosorbide dinitrate drugs with prolonged action (author's transl)].

Taking into consideration a previous work, where we experimented the pharmacological action of different products of nitrite retard and from which resulted the absolute superiority of isosorbide dinitrate, we considered interesting to repeat the experimentation with a new form of isosorbide dinitrate characterized by an action duration more prolonged in the time owing to the particular freeing of the active principle. In 20 patients free from peripheral vasculopathy it was enregistered the rheogram with derivation back-feet-big toe in base condition and at 1st, 3rd, 5th and 10th hour from the administration of Nitrosorbide Retard 20 mg. The product action, put in evidence by the appearance of the typical pulse by nitrite, begins the first hour, it reaches the maximum at the 5th hour on average and it clearly lasts until the 10th hour. Therefore it is demonstrated the practical usefulness of this product in the daily clinical medicine considered its characteristics of action rapidity, duration and steadfastness.

Adult↗
PubMed1980

Peripheral resistances in acute myocardial infarction: the use of prazosine versus isosorbide dinitrate.

Prazosine and isosorbide dinitrate have been studied in 15 patients with acute myocardial infarction complicated by heart failure. Prazosine at the first hour had a reduction of 39% of pulmonary capillary wedge pressure (PCWP), of 23% of systemic vascular resistences index (SVRI), of 20% of mean arterial pressure (AP). Isosorbide dinitrate at the first hour in a group of 7 patients had a decrease of SVRI by 19%, the cardiac index (CI) augmented by 23%, the PCWP fell by 15%, while in a group of 5 patients the drug had an increase of SVRI by 15%, a fall of 40% of PCWP and a slight decrease of CI.

Cardiac Output↗
PubMed1980

Sustained hemodynamic and antianginal effects of high dose oral isosorbide dinitrate.

Small doses of oral nitrates are ineffective antianginal agents. However, large doses of oral nitrates individually titrated to produce long-acting hemodynamic effects may be effective antianginal agents in many patients. The dose of nitrate prescribed should be titrated by blood pressure and heart rate measurements, the presence of adverse side effects, and by exercise tolerance studies before and during treatment. We would strongly recommend gradual reduction rather than an abrupt discontinuation of chronic, high-dose nitrate therapy in patients with angina pectoris to avoid possible nitrate dependence withdrawal effects. We would also recommend that continuous nitrate antianginal prophylaxis not be used in patients with angina pectoris whose symptons are readily controlled with less intensive nitrate therapy used as needed. Partial hemodynamic tolerance develops after chronic use of high-dose oral isosorbide dinitrate but the antianginal efficacy of both sublingual nitroglycerin and of high doses of oral isosorbide dinitrate is unimpaired. Patients with congestive heart failure have also had clinical and hemodynamic improvement following chronic nitrate therapy.

Administration, Oral↗