Biotransformation of Isosorbide Dinitrate in Humans

Down, W.H.; Chasseaud, L. F.; Grundy, R.K.

doi:10.1002/jps.2600630728

Cited by 76 publications

(9 citation statements)

References 20 publications

(12 reference statements)

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“…A comparison of the plasma AUC (0 to 24 h) values following oral or intravenous administration indicated almost complete absorption of the radiolabeled components from the oral doses. For ISDN (12,47) or ISMN (4734) a rapid and complete absorption has also been reported in animals and humans. The main pharmacokinetic parameters are summarized in Table 3.…”

Section: Absorption and Plasma Concentrationsmentioning

confidence: 84%

SP/W‐5186: A Novel Sulfhydryl‐Containing NO Donor

Bonn

Scharfenecker

Friehe

et al. 1998

Cardiovascular Drug Reviews

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Section: Absorption and Plasma Concentrationsmentioning

confidence: 84%

SP/W‐5186: A Novel Sulfhydryl‐Containing NO Donor

Bonn

Scharfenecker

Friehe

et al. 1998

Cardiovascular Drug Reviews

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“…ISDN is an organic nitrate vasodilator widely used for the relief of acute angina pectoris and for the prophylaxis of this condition. Its primary biotransformation products in humans are 5-ISMN and 2-ISMN (Down et al, 1974), which share the pharmacological action of the parent drug albeit at lower potencies. Recently, 5-ISMN has been developed for clinical use in angina pectoris as an addition to the available organic nitrates.…”

Section: Introduction Methodsmentioning

confidence: 99%

Saliva concentrations of isosorbide dinitrate, isosorbide 2‐mononitrate and isosorbide 5‐mononitrate.

Iw¹,

Major²,

Chasseaud³

et al. 1984

Brit J Clinical Pharma

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Correlations between saliva and plasma concentrations of isosorbide dinitrate (ISDN), and its active metabolites, isosorbide 2‐mononitrate (2‐ISMN) and isosorbide 5‐mononitrate (5‐ISMN) were examined. In the case of 5‐ISMN (r = 0.98, P less than 0.01), saliva concentrations are probably reliable indices of the plasma concentrations of this drug and their measurement should provide a useful non‐invasive procedure to assess compliance during the clinical use of products containing either ISDN or 5‐ISMN: it may also be helpful in assessing the clinical pharmacokinetics of 5‐ISMN. Less satisfactory correlations were obtained for ISDN (r = 0.84) and 2‐ISMN (r = 0.83).

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“…This long "nitrate-free" interval seems to be necessary because two vasoactive metabolites (isosorbide-2-mononitrate and isosorbide-5-mononitrate) accumulate in the plasma during continuous therapy. Isosorbide-5-mononitrate (IS-5-MN), in particular, which is the main metabolic product of ISDN and has the slowest rate of elimination [6], may be responsible for the long duration of action of ISDN and for the development of tolerance, respectively. It is now widely accepted that development of tolerance is a problem associated with the use of all organic nitrates and all routes of administration and depends on the type of compound administered, the dose, and the dosing interval [3,7].…”

mentioning

confidence: 99%

Relationship between pharmacokinetics and hemodynamic tolerance to isosorbide-5-mononitrate

Wagner

Siefert

Trenk

et al. 1990

Eur J Clin Pharmacol

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Healthy male volunteers received three different dose regimens of a controlled-release form of isosorbide-5-mononitrate (IS-5-MN; 60 mg per tablet). Dose regimen I consisted of a single daily dose of 60 mg given for 5 days. Dose regimen II was started with a dose of 60 mg, followed by 30 mg 12 h later and thereafter every 8 h. The last dose, on the 5th day was again 60 mg. In dose regimen III 60 mg followed by 30 mg 6 h later were administered every day for 5 days. The peripheral arterial and venous effects of IS-5-MN during the first and last dosing interval were followed by changes in the finger pulse curve, standing systolic blood pressure, heart rate, and venous distensibility. Plasma concentrations of IS-5-MN were measured frequently following the first and the last dose. Following dose regimen I all hemodynamic effects produced by the first dose were maintained during the study. The maximal plasma concentrations were about 400 ng/ml and the trough value, lower than 100 ng/ml. Following dose regimen II the hemodynamic effects of IS-5-MN and sublingual glyceroltrinitrate were completely abolished on the 5th day. Trough plasma concentrations were approximately 300 ng/ml during the entire study period. Following dose regimen III pronounced hemodynamic effects were seen on the 1st day. However, a significant attenuation of the hemodynamic effects was measured on the 5th day, when trough plasma concentrations were between 100 and 230 ng/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

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Biotransformation of Isosorbide Dinitrate in Humans

Cited by 76 publications

References 20 publications

SP/W‐5186: A Novel Sulfhydryl‐Containing NO Donor

SP/W‐5186: A Novel Sulfhydryl‐Containing NO Donor

Saliva concentrations of isosorbide dinitrate, isosorbide 2‐mononitrate and isosorbide 5‐mononitrate.

Relationship between pharmacokinetics and hemodynamic tolerance to isosorbide-5-mononitrate

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