Summary
An oral dose of 5 mg of14C-isosorbide dinitrate was rapidly absorbed, biotransformed and excreted by human subjects. Peak whole blood concentrations of radioactivity were reached after 1.5 to 2 hours and declined relatively slowly. The radioactivity in whole blood mainly represented metabolites, isosorbide mononitrates. The peak concentrations found were 4.5, 11.7 and 34.3 ng/ml of isosorbide dinitrate, isosorbide 2-mononitrate and isosorbide 5-mononitrate, respectively, in the blood of one subject and 5.9, 15 and 61.3 ng/ml, respectively, in the blood of another subject. However, concentrations of the metabolites declined relatively slowly during 6 h after the oral dose. Up to 99% of an oral dose of isosorbide dinitrate was excreted during 5 days, mainly in the urine of the first day (ca. 78%). The results showed that isosorbide mononitrates were available to contribute to the pharmacological action.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Berry, J.W., Carney, R., Lankford, H.: Clinical experiences with isosorbide dinitrate (Isordil).Angiology 12 254–258 (1961)
Russek, H.I.: The therapeutic role of coronary vasodilators: glyceryl trinitrate, isosorbide dinitrate and pentaerythritol tetranitrate. Amer. J. med. Sci.252 9–19 (1966)
Goldstein, R.E., Rosing, D.R., Redwood, D.R., Beiser, G.D., Epstein, S.E.: Clinical and circulatory effects of isosorbide dinitrate. Circulation43 629–640 (1971)
Bogaert, M.G.: Organic nitrates in angina pectoris. Arch. Int. Pharmacodyn.196 suppl, 25–34 (1972)
Göbbeler, K.H.: Gaschromatographische Bestimmung von Isosorbiddinitrat im Blut mit Hilfe des Electron-capture-Detektors. Pharm. Ztg. (Frankfurt)116 961–962 (1971)
Davidson, I.W.F., DiCarlo, F.J., Szabo, E.I.: Gas chromatographic separation and detection of pentaerythritol nitrates and other organic nitrate esters. J. Chromatog.57 345–352 (1971)
Rosseel, M.T., Bogaert, M.G.: GLC determination of nitroglycerin and isosorbide dinitrate in human plasma. J. pharm. Sci.62 754–758 (1973)
Needleman, P., Lang, S., Johnson, Jr., E.M.: Organic nitrates: Relationship between biotransformation and rational angina pectoris therapy. J. Pharmacol. exp. Ther.181 489–497 (1972)
Chasseaud, L.F., Hawkins, D.R., Cameron, B.D., Fry, B.J., Saggers, V.H.: The metabolic fate of bentazon in the rat. Xenobiotica2 269–276 (1972)
Patterson, M.S., Greene, R.C.: Measurement of low energy beta-emitters in aqueous solution by liquid scintillation counting of emulsions. Analyt. Chem.37 854–857 (1965)
Lewis, J.D.: A modified plastic bag combustion technique for the radioassay of14C and3H in biological tissue. Int. J. appl. Radiat.23 39–40 (1972)
Dobbs, H.E.: Oxygen flask method of the assay of tritium-carbon-14-and sulphur-35-labelled compounds. Analyt. Chem.35 783–786 (1963)
Down, W.H., Chasseaud, L.F., Grundy, R.K.: Biotransformation of isosorbide dinitrate in humans. J. pharm. Sci.63 1147–1149 (1974)
Needleman, P., Krantz, Jr., J.C.: The biotransformation of nitroglycerin. Biochem. Pharmacol.14 1225–1230 (1965)
Needleman, P., Hunter, Jr., F.E.: The transformation of glyceryl trinitrate and other nitrates by glutathione-organic nitrate reductase. Molec. Pharmacol.1 77–86 (1965)
Davidson, I.W.F., Miller, Jr., H.S., DiCarlo, F.J.: Pharmacodynamics and biotransformation of pentaerythritol tetranitrate in man. J. pharm. Sci.60 274–277 (1971)
Litchfield, M.H.: Aspects of nitrate ester metabolism. J. pharm. Sci.60 1599–1607 (1971)
Chasseaud, L.F.: The nature and distribution of enzymes catalysing the conjugation of glutathione with foreign compounds. Drug. Metab. Rev.2 185–220 (1973)
Johnson, Jr., E.M., Harkey, A.B., Blehm, D.J., Needleman, P.: Clearance and metabolism of organic nitrates. J. Pharmacol. exp. Ther.182 56–62 (1972)
Russek, H.I., Funk, Jr., E.H.: Comparative responses to various nitrates in the treatment of angina pectoris. Postgrad. Med.31 150–155 (1962)
Wendt, R.L.: Systemic and coronary vascular effects of the 2- and 5-mononitrate esters of isosorbide. J. Pharmacol. exp. Ther.180 732–742 (1972)
Bogaert, M.G., Rosseel, M.T.: Vascular effects of the dinitrate and mononitrate esters of isosorbide, isomannide and isoidide. Arch. Pharmacol.275 339–342 (1972)
Sisenwine, S.F., Ruelius, H.W.: Plasma concentrations and urinary excretion of isosorbide dinitrate and its metabolites in the dog. J. Pharmacol. exp. Ther.176 296–301 (1971)
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Chasseaud, L.F., Down, W.H. & Grundy, R.K. Concentrations of the vasodilator isosorbide dinitrate and its metabolites in the blood of human subjects. Eur J Clin Pharmacol 8, 157–160 (1975). https://doi.org/10.1007/BF00567108
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00567108