Plasma Isosorbide Dinitrate Research Articles

Influence of exercise on plasma concentrations of isosorbide dinitrate.

As the fall in hepatic blood flow caused by exercise is expected to decrease the elimination of high extraction drugs, the influence of exercise on the fate of the anti-anginal drug isosorbide dinitrate has been assessed. Isosorbide dinitrate 10 mg was given orally, after an overnight fast, on 2 different days to 7 healthy volunteers and the plasma concentrations of the parent compound and its mononitrate metabolites were measured. Heavy bicycle exercise from the 45th to the 105th min after intake of the drug on one of the experimental days did not change the plasma isosorbide dinitrate concentrations as compared to those on the rest day. The concentrations of both mononitrates were lower on the exercise day, but the difference was already present before the exercise started.

Isosorbide dinitrate in plasma and dialysate during haemodialysis.

In 10 patients with end stage renal disease on regular haemodialysis the plasma concentrations and dialyzer clearance of isosorbide dinitrate (ISDN) were determined after an oral dose of a retarded release formulation of 60 mg ISDN. The maximal plasma concentration of ISDN 2-7 h after oral administration was higher (14 ng/ml) than has been reported in healthy volunteers. The haemodialyzer clearance of ISDN was 92.4 ml/min at a blood flow of 200 ml/min and dialysate flow of 500 ml/min. During a 5-h haemodialysis an average of 0.3 mg ISDN was removed from the patient's circulation, representing about 0.5% of the administered dose and about 3% of the available drug in the circulation. No influence of haemodialysis on the plasma level of ISDN was found.

Prolonged plasma half-life after oral isosorbide dinitrate in patients with angina pectoris.

The plasma concentration of isosorbide dinitrate (ISDN) was monitored up to 24 h after a chronic oral dose of 60 mg in six patients with coronary artery disease. A terminal half-life of 7.7 +/- 2.6 h (mean +/- s.d.) was observed. The presence of this prolonged disappearance phase provided at least a partial explanation for the observed accumulation of ISDN in plasma after chronic dosing on a six hourly regimen.

Use of Isosorbide Dinitrate Saliva Concentrations for Biopharmaceutical Investigations

The concentration of isosorbide dinitrate in paired samples of plasma and mixed saliva was monitored for up to 24hr after oral administration of 60mg of sustained-release isosorbide dinitrate to eight healthy volunteers. Measured isosorbide dinitrate plasma concentrations were mainly in the range of 0.1-10ng/ml. Isosorbide dinitrate was excreted into saliva resulting in a mean (±SD) saliva–plasma concentration ratio of 0.68±0.37. A significant correlation between concentrations of isosorbide dinitrate in saliva and plasma was found (p<0.01). The sustained-release properties of the administered formulation were confirmed from the concentrations of isosorbide dinitrate found in both saliva and plasma. Saliva-plasma ratios were independent of the absolute concentrations of isosorbide dinitrate but showed a slight tendency to decrease with time. The principal factor relating saliva and plasma isosorbide dinitrate concentrations appeared to be the degree of plasma protein binding of the drug.

Measurement of plasma concentrations of isosorbide dinitrate.

Concentrations of the vasodilator isosorbide dinitrate (ISDN) in human plasma can be measured with good sensitivity (about 0.2--0.5 ng ml-1) using electron-capture gas chromatography after a one-stage extraction. The mean recovery of ISDN from plasma was 83 per cent +/- 9 standard deviation (S.D.). The precision of the method for the measurement of ISDN in plasma ranged from +/- 14 per cent at 1 ng ml-1 to +/- 7 per cent at 5 ng ml-1 to +/- 4 per cent at 50 ng ml-1. The 95 per cent confidence limits of the least-squares regression calibration line forced through the origin were +/- 100 percent at 1 ng ml-1, +/- 11 per cent at 10 ng ml-1, and +/- 8 per cent at 30 ng ml-1. The method has been used to assay many samples withdrawn after doses of drug at therapeutic levels to normal subjects.

Plasma concentrations of isosorbide dinitrate after cutaneous and sublingual doses to human subjects.

After application of 100 mg (nominal dose) isosorbide dinitrate as an ointment to the skin of human subjects, mean drug concentrations were 1 to 2 ng/ml for 1.5 hour and reached a peak of 6.2 ng/ml at 6 hours. Thereafter, mean concentrations declined slowly to 2.9 ng/ml at 12 hours and 1.2 ng/ml at 24 hours. After a sublingual dose of 5 mg isosorbide dinitrate, mean drug concentrations reached a peak of 15.9 ng/ml at 0.5 hour and declined with a half-life of about 50 minutes. The mean bioavailability of isosorbide dinitrate from the ointment was estimated as 30 per cent of that from the sublingual tablet when corrected for differences in dose/body weight ratio. The results demonstrate that concentrations of isosorbide dinitrate in plasma can be maintained for relatively long periods when the drug is applied to the skin.

Quantitative Determination of Isosorbide Dinitrate and Two Metabolites in Plasma

A GLC method for the determination of plasma isosorbide dinitrate and two metabolites, isosorbide 2-mononitrate and isosorbide 5-mononitrate, is described. The three substances are extracted from alkalinized plasma with ether. Quantitation is effected by electrón-capture detection after GLC separation with a 30% SE-30 column. The unusually heavy liquid phase loading is necessary to eliminate irreversible adsorption on the solid support. The electron-capture detector provides excellent sensitivity and specificity because of the electronegative nature of the nitric ester. The method was used to study the blood levels of isosorbide dinitrate and two metabolites in four beagle dogs after single oral doses of 40mg of isosorbide dinitrate and in two human volunteers after a sublingual dose of 10mg of isosorbide dinitrate.

Plasma Isosorbide Dinitrate Concentrations in Human Subjects after Administration of Standard and Sustained-Release Formulations

After sublingual administration of 5 mg of isosorbide dinitrate, mean plasma concentrations (+/-SD) peaked (8.9+/-3.1 ng/ml) at 15 min after dosing and declined with a half-life of 30 min. After oral administration of 5 mg, mean concentrations peaked (3.1+/-0.7 ng/ml) at 30 min and declined with a half-life of 40 min. After oral administration of 20 mg in a sustained-release tablet, mean concentrations initially peaked (1.4+/-1.2 ng/ml) at 40 min, declining to 0.9+/-0.5 ng/ml after 8 hr. Mean concentrations were maintained above half the mean peak level during 10 hr. Because of probable rapid first-pass metabolism, the bioavailability of isosorbide dinitrate after administration of the oral dose of the standard tablet was 58% of that from the sublingual dose, and the bioavailability from the sustained-release tablet was 47% of that from the sublingual dose of the standard tablet. The time course of mean plasma concentration data could be described by a one-compartment model; but a more complex model, taking the pass effect into account, probably is needed for a better description of the pharmacokinetics of isosorbide dinitrate.

Electron-capture GLC determination of nanogram to picogram amounts of isosorbide dinitrate.

A GLC method for the determination of plasma isosorbide dinitrate using electron-capture detection is described. The organic nitrates are especially suited for electron-capture detection if the detector temperature is optimized for maximum sensitivity, e.g., 175 degrees. Proper maintenance of the detector and column assures reproducible data in the low nanogram range. The extraction procedure described is simple, efficient, and expedient for processing large numbers of samples. The method was used to study plasma levels in four human volunteers after a single dose of a 5-mg chewable isosorbide dinitrate tablet. Concentration levels of isosorbide dinitrate as low as 0.5 ng/ml of plasma can be measured by this procedure.

Simultaneous measurement of plasma isosorbide dinitrate, isosorbide-2-mononitrate, and isosorbide-5-mononitrate by gas-liquid chromatography.

Journal Article Simultaneous measurement of plasma isosorbide dinitrate, isosorbide-2-mononitrate, and isosorbide-5-mononitrate by gas-liquid chromatography. Get access L Richard, L Richard Search for other works by this author on: Oxford Academic Google Scholar G Klein, G Klein Search for other works by this author on: Oxford Academic Google Scholar J M Orr J M Orr Search for other works by this author on: Oxford Academic Google Scholar Clinical Chemistry, Volume 22, Issue 12, 1 December 1976, Pages 2060–2061, https://doi.org/10.1093/clinchem/22.12.2060 Published: 01 December 1976

GLC Determination of Nitroglycerin and Isosorbide Dinitrate in Human Plasma

A procedure is described for the identification and quantitative determination of nitroglycerin and isosorbide dinitrate in plasma. The nitrates are extracted from plasma with ethyl acetate and measured by GLC with electron-capture detection. Quantitation is done using an internal standard. The lower limit of sensitivity for both substances is around 0.5 ng./ml. Results obtained with this method in humans are given.