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PubMed1977

[Treatment of infantile hydrocephalus with isosorbide dinitrate (author's transl)].

Eighteen of infantile hydrocephalus have been treated with isosorbide dinitrate. Pharmacology of this compound is considered. It appears that completely dinitrated isosorbide is the major metabolite. Isosorbide may be effective in a variable proportion of various types of infantile hydrocephalus. Results of isosorbide dinitrate therapy in children with "communicating" and "noncommunicating" hydrocephalus are reported. Treatment was monitored by simple measurements, and it's toxicity proved to be scanty.

Administration, Oral↗
PubMed1985

[Transcutaneous application of nitroglycerin and isosorbide dinitrate versus placebo: effect in myocardial ischemia].

The effect of nitroglycerin ointment (30 mg) and isosorbide dinitrate ointment (100 mg) versus placebo on exercise capacity has been investigated in 12 patients. All had angina pectoris and coronary artery disease documented by coronary angiography. Nitroglycerin and isosorbide dinitrate ointment produced a significant increase in exercise capacity, without any significant difference in the beneficial effect of the two. Stress-induced changes of the ST-segment in the electrocardiogram decreased by 65% after nitroglycerin ointment and by 41% after isosorbide dinitrate ointment, compared to placebo. These results indicate that nitroglycerin and isosorbide dinitrate ointment reduce stress-induced myocardial ischemia at similar work loads.

Administration, Topical↗
PubMed1977

Plasma concentrations of isosorbide dinitrate after oral administration of a sustained-release formulation to human subjects.

1. A peak of mean plasma concentrations of isosorbide dinitrate of 5.8 ng/ml was reached at 0.5 h after a single oral dose of 5 mg in a standard tablet formulation. Thereafter mean concentrations declined with a half-life of about 48 min. 2. A peak of mean concentrations of isosorbide dinitrate of 3.2 ng/ml was reached at 2--4 h after a single oral dose of 20mg in a sustained-realease capsule formulation (Iso Mack Retard). Thereafter mean concentrations declined by about twofold during 6 h and were still detectable at 12 h after dosing. 3. When corrected by dose/bodyweight variations, the mean area under the isosorbide dinitrate plasma concentration curve from the sustained-release capule was 76% of that from the standard tablet and this formulation-related difference in bioavailability was statistically significant (p less than 0.05). 4. The results showed that sustained-release formulation is a useful way to maintain plasma concentrations of isosorbide dinitrate for several hours.

Adult↗
PubMed1983

Bioavailability of isosorbide dinitrate and its two mononitrate metabolites from sustained-release formulations.

Plasma concentrations and bioavailability of isosorbide dinitrate (ISDN) and its active metabolites isosorbide 2-mononitrate (2-ISMN) and isosorbide 5-mononitrate (5-ISMN) from two sustained-release formulations and one standard-release formulation of isosorbide dinitrate were compared. Means of peak drug concentrations of ISDN, 2-ISMN, and 5-ISMN after administration of the 20-mg sustained-release formulation were 5.5, 24.4, and 129.1 ng/ml, respectively, at 3.1, 4.2, and 4.5 h; after the 40-mg sustained-release formulation, they were 10.9, 44.0, and 214.5 ng/ml, respectively, at 4.2, 6.3, and 6.7 h; and after the 20-mg standard formulation, they were 19.1, 34.7, and 159.2 ng/ml, respectively, at 0.5, 1.0, and 1.5 h. As might be expected, peak concentrations and their times of occurrence were statistically significantly different when results from the sustained-release formulation were compared to those from the standard formulation. Plasma drug concentrations were detectable for longer after administration of the sustained-release formulations. The extent of bioavailability of ISDN, 2-ISMN, and 5-ISMN from the three formulations as estimated from the areas under the plasma drug concentration - time curves were not statistically significantly different (p greater than 0.05). The ratios for relative drug bioavailability from the respective formulations were similar whether ISDN, 2-ISMN, or 5-ISMN data were used for calculation. Reasons are discussed for the biphasic decline of plasma ISDN concentrations (half-lives 26 min and 5.1 h) obtained after administration of the standard-release formulation.

Adolescent↗
PubMed1983

Does isosorbide-5-mononitrate influence left ventricular relaxation?

In 25 patients, 21 of whom had coronary heart disease, left ventricular high-fidelity pressure measurements, M-mode-echocardiograms, phono- and electrocardiograms were carried out before and 20 min after peroral administration of 50 mg isosorbide-5-mononitrate. Left ventricular relaxation was assessed by the isovolumic relaxation time, left ventricular max negative dP/dt, the time constant, T, of left ventricular pressure decay during the isovolumic relaxation period, and peak fall of meridional wall stress (max negative dS/dt). Following isosorbide-5-mononitrate the heart rate was not altered; left ventricular systolic pressure, however, decreased from 129 to 117 mmHg (P less than 0.001) as did the end-diastolic pressure from 15 to 8 mmHg (P less than 0.001). The left ventricular end-diastolic diameter decreased from 53 to 50 mm (P less than 0.001) and left ventricular peak stress from 182 to 142 X 10(3) dynes/cm2 (P less than 0.001). Max dP/dt and left ventricular systolic shortening remained essentially unchanged, indicating that contractility during the isovolumic-contraction phase as well as during ejection was not influenced. Max negative dP/dt, max negative dS/dt, and the isovolumic relaxation time also remained unchanged. T, however, decreased from 54 to 45 ms (P less than 0.001). We conclude that peroral administration of isosorbide-5-mononitrate is followed by a decrease in pre- and afterload, but also by an increase in the speed of left ventricular relaxation as evidenced by the diminished T. Since T has been reported as being load-independent, its decrease either reflects a genuine effect of isosorbide-5-mononitrate on left ventricular relaxation or results from a diminution of residual ischemia.

Adult↗
PubMed1983

High-dosage isosorbide dinitrate therapy for angina.

We investigated the possibility that high dosages (480 mg/d) of isosorbide dinitrate might reduce the frequency of angina attacks in selected patients who had not responded to low dosages of the drug (40 mg/d), and that the patients could tolerate the high levels of medication and maintain their responsiveness over the long term. In the single-blind phases of this trial 24 patients with grade 3 stable angina pectoris were given a placebo for 4 weeks and then increasing doses of isosorbide dinitrate for a further 6 weeks. The 19 patients who both responded to and tolerated high doses of the drug kept taking 480 mg/d for an average of 1 year. The average weekly rate of angina attacks fell by 74%, from 6.05 in the placebo phase to 1.6 during long-term active treatment (p less than 0.01). Nitroglycerin consumption decreased accordingly. The patients' assessments of their levels of activity and well-being and their angina thresholds showed improvement among most of them. The trend of angina frequency was stable in 12 cases, downward in 6 and upward in only 1 case. Exercise performance as evaluated by a graded treadmill test showed a small but nonsignificant improvement of 18%. It was concluded that some patients who do not respond to the antianginal action of low-dosage isosorbide dinitrate and cannot be given beta-blockers may respond to high dosages and tolerate them for over a year. Isosorbide dinitrate may be clinically useful in patients with coronary heart disease even though their exercise performance is not significantly improved.

Adult↗
PubMed1993

Bioavailability and pharmacokinetics of a new isosorbide dinitrate spray preparation in healthy volunteers.

In the course of this study the bioavailability and pharmacokinetic profile of a newly developed 2.5 mg (per valve release) oral isosorbide dinitrate (ISDN, CAS 87-33-2) spray preparation (Isoket Spray) were determined and compared with the results for an already marketed reference spray preparation following single application. For this purpose, the test and reference spray were examined in 18 healthy volunteers according to a randomized 2-way cross-over design. Blood samples were collected during 12 h p.a. and plasma concentrations of ISDN and its metabolites isosorbide-2-mononitrate (IS-2-MN) and isosorbide-5-mononitrate (IS-5-MN) were quantified by a GC-method. Both sprays showed mean maximum concentrations of ISDN in plasma of nearly 18 ng/ml about 7 min after drug intake with arithmetic mean values for the areas under the curve AUC0-12 of 7.01 (test spray) and 7.30 h.ng/ml (reference spray). For the metabolic products IS-2-MN and IS-5-MN (values for the reference spray in brackets) the corresponding maximum concentrations were 4.15 (4.21) ng/ml and 16.1 (15.9) ng/ml, respectively, and for the areas under the curve AUC0-12 values of 9.75 (9.92) h.ng/ml for IS-2-MN and 104.3 (99.7) h.ng/ml for IS-5-MN in the mean were calculated. Statistical evaluation of all pharmacokinetic parameters revealed bioequivalence between the two preparations. Typical side-effects known and described under isosorbide dinitrate therapy were also observed in this study.

Adolescent↗
PubMed1993

Effect of enalapril, hydralazine plus isosorbide dinitrate, and prazosin on hospitalization in patients with chronic congestive heart failure. The V-HeFT VA Cooperative Studies Group.

BACKGROUND: Hospitalization of persons with congestive heart failure for recurrent heart failure or other complications is common. METHODS AND RESULTS: Male patients aged 18-75 with chronic heart failure were randomized in two sequential trials designed to study the efficacy of vasodilator therapy. Patients were evaluated every 3 months, and information regarding hospitalizations between visits was obtained from the patient, his family, and/or hospital records. Hospitalization data also were obtained for patients who had died between scheduled clinic visits. Hospitalizations were not recorded if a patient died during transit to the hospital or in the hospital emergency department before admission. In Vasodilator-Heart Failure Trial (V-HeFT) I, no significant difference in number of patients hospitalized or number of hospitalizations was noted among the treatment groups, although there was a trend for fewer and delayed cardiac hospitalizations in the hydralazine plus isosorbide dinitrate arm in which the survival was greater. In V-HeFT II, no difference in hospitalizations was apparent between the enalapril and hydralazine plus isosorbide dinitrate arms. Univariate predictors of hospitalization for all causes were reduced peak oxygen consumption (VO2) during exercise (p < 0.0001), reduced exercise duration (p < 0.0001), increased cardiothoracic ratio on chest radiograph (p < 0.0001), increased age (p < 0.03), and use of antiarrhythmic drugs (p < 0.013), whereas multivariate predictors were reduced peak VO2 (p < 0.0001), use of antiarrhythmic drugs (p < 0.015), and increased cardiothoracic ratio (p < 0.03). Univariate predictors of hospitalization for heart failure were peak VO2 (p < 0.0001), LVEF (p < 0.0001), reduced exercise duration (p < 0.0001), elevated cardiothoracic ratio (p < 0.0001), and elevated plasma norepinephrine (p < 0.0001). Multivariate predictors were exercise duration (p < 0.0001), LVEF (p < 0.04), elevated cardiothoracic ratio (p < 0.03), plasma norepinephrine (p < 0.0005), and coronary artery disease (p < 0.02). Time to first hospitalization, cause specific or overall, was considerably shorter for patients with baseline peak VO2 < 10 mL.kg-1 x min-1 compared with those with peak VO2 > 15 mL.kg-1 x min-1. CONCLUSIONS: Despite better survival in patients randomized to hydralazine plus isosorbide dinitrate compared with placebo and better survival in patients randomized to enalapril compared with hydralazine plus isosorbide dinitrate, no significant differences between the treatment groups were apparent in the incidence of hospitalization or time to first hospitalization for congestive heart failure, for cardiac reasons other than congestive heart failure, or for other causes. V-HeFT I and V-HeFT II data demonstrate no treatment effect on hospitalization, perhaps reflecting in part the effectiveness of the Veterans Affairs special heart failure clinics in dealing with worsening heart failure on an outpatient basis. Identification of predictors of hospitalization were similar in both studies.

Drug Therapy, Combination↗
PubMed1995

[Acute effects of isosorbide mononitrate on blood circulation and myocardial ischemia in patients with coronary atherosclerosis].

PURPOSE: To evaluate the acute effects of isosorbide mononitrate on circulation, cardiac function and left ventricular segmental motility in patients with isquemic heart disease due to coronary artery disease. METHODS: Twenty-four patients with ischemic heart disease, 10 women, with mean age of 58 years, were studied during cardiac catheterization, at baseline condition and 5min after intravenous infusion of 0.3mg/kg of isosorbide mononitrate. RESULTS: After infusion of isosorbide mononitrate there were significant reduction in mean right atrial pressure no mean pulmonary artery pressure (< 0.0001), left ventricular and diastolic pressure (p < 0.004), left ventricular systolic pressure (p < 0.002), maximum (p < 0.002) and mean (p < 0.008) aortic pressure, and left ventricular systolic volume (p < 0.004), as well as significant increase in the left ventricular ejection fraction (p < 0.001) and mean velocity of circunferential fibers shortening (p < 0.001). There was no significant modification of minimum aortic pressure, heart rate, cardiac output nor of left ventricular and diastolic volume. With respect of segmental motility of the left ventricle after medication, 38 kypokinetic segments normalized their motility, 4 akinetic segments remained intact, and of the 21 dyskinetic segments, 6 normalized, 8 became hypokinetic and 7 remained dyskinetic. CONCLUSION: Isosorbide mononitrate, when used as intravenous infusion, have a rapid and direct effect on systemic and pulmonary circulation, and improving segmental motility and left ventricular performance in patients with impaired left ventricular motility caused by ischemic heart disease.

Adult↗
PubMed1977

Gas-liquid chromatographic determination of isosorbide dinitrate in tablets.

A gas-liquid chromatographic (GLC) method is described for determining isosorbide dinitrate (ISDN) in tablets. ISDN is extracted from tablet excipients by a 2-phase system composed of water-ethyl ether, and detected and quantitated with a flame ionization detector after separation from the internal standard (glyceryl tributyrate) on a 3% OV-210 column. Ten replicate assays on 2 different batches of tablets, each containing 5 mg ISDN, gave coefficients of variation of 1.16 and 1.48%, respectively. Comparison of results obtained for tablets containing 5, 10, and 40 mg ISDN, and for diluted isosorbide dinitrate raw material containing 25% ISDN, showed good correlation among the GLC, USP colorimetric, and USP polarographic procedures. Assay of synthetic mixtures containing ISDN, isosorbide-2-mononitrate, and isosorbide-5-mononitrate demonstrated that the GLC procedure is specific for ISDN, whereas the USP polarographic procedure is subject to interference from the mononitrates.

Chromatography, Gas↗
PubMed1997

Effect of isosorbide on distortion-product otoacoustic emissions and endocochlear DC potential in experimentally induced hydropic ears.

The effects of isosorbide on distortion-product otoacoustic emissions (DPOAEs) and endocochlear DC potential (EP) were examined in experimentally induced endolymphatic hydropic ears and untreated control ears using 20 albino guinea pigs. DPOAEs and EP in the hydropic ears decreased after obliteration of the endolymphatic duct and sac. The administration of isosorbide restored DPOAEs to the normal level, whereas EP was further reduced. In control ears there was no significant change in DPOAEs and EP after the administration of isosorbide. The results obtained in the present study indicate that the effect of isosorbide on DPOAEs is different from that on EP, and the recovery of DPOAEs in hydropic ears is not a secondary phenomenon due to the recovery of EP.

Acoustic Stimulation↗
PubMed1998

[Efficacy of isosorbide in aerosol form in the management of hypertensive crisis in severe preeclampsia].

In this assay, we evaluated the utility of isosorbide given by a sprayer in the management of hypertensive crisis of severe preeclampsia. 36 pregnant women with severe preeclampsia received fluid therapy and were randomly dividend in two groups of 18 patients each. Group A, received isosorbide in spray 1.25 mg when admitted and a second dose 10 minutes after if mean arterial blood pressure decreased less than 15%. and group B, in whom 4 g of magnesium sulphate was infused in one hour and then 1 g each hour for a maximum of five hours. In all patients blood pressure, proteinuria, fetal and maternal heart rate and Apgar score at minute and five minutes were obtained. In Group A 13 patients had a significative blood pressure reduction with one application and 5 needed a second one (p < 0.002). fetal (p < 0.005), and maternal (p < 0.005) heart rate also had a significative reduction. Whereas three patients in Group B did not respond and the rest had a poor blood pressure control (p > 0.05) with no changes in fetal and maternal heart rate. No patient developed eclampsia. When compared both groups, there were a significative difference for blood pressure (p < 0.005), fetal heart rate (p < 0.002), maternal heart rate (p < 0.05) and Apgar at minute (p < 0.01) in isosorbide's group. Our data suggest that isosorbide given by a sprayer is effective and safer in the management of the hypertensive crisis of severe preeclampsia.

Adult↗
PubMed1994

Dose-Related Hepatic Blood Flow Effects Differentiate Nicorandil, Hydralazine, and Isosorbide Dinitrate in Healthy Subjects.

Dose response on hepatic blood flow of nicorandil (2.5, 5, and 10 mg), isosorbide dinitrate (5, 15, and 40 mg), and hydralazine (10, 25, and 50 mg) was assessed in 18 healthy subjects (6 per drug) using a three-period crossover design. Indocyanine green clearance was used to estimate hepatic blood flow before and at two timepoints after dosing. Greater hepatic blood flow changes occurred 90 (than 30) min after nicorandil and isosorbide dinitrate, and 60 (than 150) min after hydralazine. Nicorandil (mixed vasodilator) decreased hepatic blood flow by minus sign13 plus minus 4% (p < 0.05), minus sign15 plus minus 7%, and minus sign21 plus minus 6% (p < 0.05) (mean plus minus standard error of the mean) after 2.5, 5, and 10 mg, respectively; blood pressure was not reduced and heart rate was unchanged. Individual changes correlated poorly with plasma nicorandil concentrations. Isosorbide dinitrate (predominant venodilator) decreased hepatic blood flow by minus sign23 plus minus 9%, minus sign27 plus minus 5% (p < 0.05), and minus sign26 plus minus 7% (p < 0.05) after 5, 15, and 40 mg, respectively; blood pressure decreased (8--12 mm Hg) and heart rate increased (8 beats min(minus sign1)). Hydralazine (arterial dilator) increased hepatic blood flow by 29 plus minus 16%, 32 plus minus 11% (p < 0.05), and 33 plus minus 26% after 10, 25, and 50 mg, respectively; blood pressure was unchanged and heart rate increased (16 beats min(minus sign1)). Hepatic vascular resistance increased after nicorandil and isosorbide dinitrate but decreased after hydralazine. As assessed by hepatic blood flow response, nicorandil behaves more like a predominant venodilator than a direct arterial dilator. Dose and time variables were important to understanding the overall hemodynamic profile of each drug.

Journal Article↗
PubMed1976

Polarographic determination of isosorbide dinitrate.

Isosorbide dinitrate and two isomeric isosorbide mononitrates are shown to be polarographically reducible in aqueous sodium perchlorate or potassium chloride solution. The current, measured at -1.6 v, versus the saturated calomel electrode is proportional to the concentration of organic nitrate in the 10-100-mug/ml range. Inorganic nitrate produces no interference. However, the mononitrate isomers produce an additive response to isosorbide dinitrate and cannot be determined individually. The polarographic method is applicable to single-tablet assay for content uniformity determination, with precision and accuracy comparable to automated colorimetric analysis. Comparison is made between replicate analyses obtained polarographically and by IR and automated colorimetric analysis for six different commercially available formulations. The polarographic determination is sensitive, specific for nitrate esters, precise, requires little sample preparation, and utilizes relatively inexpensive apparatus.

Autoanalysis↗
PubMedDate not supplied

Pharmacokinetics of isosorbide dinitrate after intravenous infusion in human subjects.

Plasma concentrations of isosorbide dinitrate have been measured after intravenous infusion of drug at a rate of 5.0 mg h-1 for 150 min and after single equal oral doses of 12.5 mg of drug in solution to two normal human subjects. During the infusion, uneven plateau concentrations were approached after 30 min. The calculated average steady-state plasma levels were 258 ng ml-1 and 514 ng ml-1 in the two subjects respectively. The half-life of elimination of isosorbide dinitrate after termination of the infusion was 9--10 min. After oral doses, peak plasma levels of 26.6 ng ml-1 and 12.7 ng ml-1 occurred at 10 min and 20 min in the two subjects respectively. The terminal half-life of drug after the oral doses was much longer than the elimination half-life (about 10 min), and was associated with the absorption phase. Fairly good agreement was obtained between the observed concentrations and those predicted by a one-compartment open model. The systemic availability of isosorbide dinitrate after the oral doses was up to only 3 per cent of the equal doses infused, indicating that presystemic elimination processes accounted for very large proportions of the oral doses. The systemic clearances of drug after infusion of 0.32 l min-1 and 0.16 l min-1 were unexpectedly low for a drug of reported high liver extraction ratio.

Adult↗
PubMedDate not supplied

Determination of isosorbide dinitrate biotransformation in various tissues of the rabbit by capillary column gas-liquid chromatography.

A selective and sensitive capillary column gas-liquid chromatographic procedure has been developed for the simultaneous determination of isosorbide dinitrate (ISDN) and its mononitrate metabolites in rabbit blood and tissue homogenates. The method has a limit of detection of 0.1 ng ml-1 for ISDN, 1 ng ml-1 for isosorbide 5-mononitrate (5-ISMN), and 2 ng ml-1 for isosorbide 2-mononitrate (2-ISMN). The day-to-day coefficients of variation were 2.5, 6.8, and 11.3 per cent for ISDN, 5-ISMN, and 2-ISMN, respectively. The within-day coefficients of variation were 2.7, 4.9 and 6.5 per cent for ISDN, 5-ISMN, and 2-ISMN, respectively. The procedure was used to determine the biotransformation of ISDN (2 X 10(-7) M) to 5-ISMN and 2-ISMN by various rabbit tissue homogenates. The relative rate of biotransformation of ISDN was liver greater than lung approximately equal to intestine greater than kidney greater than blood approximately equal to skeletal muscle, with the lung and intestine homogenates being about two-thirds as active as liver homogenates. These results indicate that extrahepatic biotransformation of ISDN, especially by lung and intestine, may contribute to the systemic clearance of ISDN in the rabbit.

Animals↗
PubMed1990

Assay of glyceryl trinitrate, isosorbide dinitrate, and their metabolites in plasma by large-bore capillary column gas-liquid chromatography.

Two large-bore capillary columns, one with dimethyl polysiloxane (HP-1) as the stationary phase and the other with phenyl (50 per cent) methyl (50 per cent) polysiloxane (DB-17), were used to develop gas-liquid chromatographic (GLC) assays for measuring isosorbide dinitrate (ISDN), glyceryl trinitrate (GTN), and their metabolites. ISDN, isosorbide-2-mononitrate (2-ISMN), and isosorbide-5-mononitrate (5-ISMN) in plasma, ranging in concentration from 1 to 300 nM, and GTN, glyceryl-1,2-dinitrate (1,2-GDN), and glyceryl-1,3-dinitrate (1,3-GDN), ranging in concentration from 3 to 60 nM in plasma, were analysed on both columns. GLC analysis yielded baseline resolution of the analytes. The method using the dimethyl polysiloxane column gave a lower limit of detectability for GTN of 0.75 nM (signal/noise (s/n) = 2), and the procedure using the phenyl-methyl column provided a lower limit of detectability for ISDN of 81 pM (s/n = 2). The large-bore column GLC procedures exhibited shorter retention times for both ISDN and GTN than those previously reported for capillary-column assays. The chromatographic resolution of analytes and column efficiency of the large-bore capillary columns were comparable to the results previously found using capillary-column GC. The assays for ISDN and GTN have been shown to be appropriate for pharmacokinetic studies in volunteers and patients. We determined that the HP-1 column is appropriate for the analysis of GTN and metabolites, and the DB-17 column is suitable for analysis of ISDN and its metabolites. We conclude that the use of large-bore capillary columns provides rapid and reliable GLC assays for organic nitrates.

Chromatography, Gas↗
PubMed1992

Plasma disposition and hemodynamic effects of a single oral dose of isosorbide dinitrate in human males and females.

The goal of the present work was to determine the plasma disposition and hemodynamic effects of isosorbide dinitrate (ISDN) in human males and females. Fourteen healthy human volunteers took part in the study; seven males, 21.7 +/- 2.5 y (SD), and seven females, 20.7 +/- 3.4 y. Measurements of forearm blood flow (FBF), vascular conductance (FVC), and venous capacitance (Cv) were obtained by venous occlusion plethysmography, whereas blood pressure was measured by automatic sphygmomanometry. Blood samples were taken through a catheter placed in the antecubital vein at 0, 15, 30, 45, 60, 90, 120, 360, 480, 720, and 1440 min following a single 10 mg oral dose of ISDN. Plasma concentrations of ISDN and its mononitrate metabolites, isosorbide-2-mononitrate (2-ISMN) and isosorbide-5-mononitrate (5-ISMN), were determined by large bore capillary column gas-liquid chromatography. Hemodynamic measurements were made at corresponding experimental times up to 480 min. No differences were observed in the disposition of ISDN, 2-ISMN or 5-ISMN between the male and female volunteers. In addition, the plasma concentrations of ISDN and its mononitrate metabolites did not consistently correlate with the hemodynamic changes of the individual subjects. Diastolic blood pressure was significantly decreased for a 0.5 h period starting at 30 min, which was the time at which plasma ISDN concentrations peaked, and which preceded the time when the plasma concentrations of 2-ISMN and 5-ISMN were maximal. These observations indicate that, for a single 10 mg oral dose of ISDN, there were no gender-dependent differences in the plasma disposition of the parent drug or its mononitrate metabolites, and the vascular changes responsible for the decrease in diastolic blood pressure in these volunteers occurred in vascular beds other than those of skeletal muscle as represented by forearm blood flow.

Administration, Oral↗