PHARMACOKINETIC ASPECTS OF ISOSORBIDE-5-MONONITRATE IN DOGS

  • 1 January 1984
    • journal article
    • research article
    • Vol. 228  (1) , 235-239
Abstract
Pharmacokinetic data of isosorbide-5-mononitrate (IS-5-MN) in dogs were obtained and correlated 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 [an antianginal drug], 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 At defined times blood samples were withdrawn from the vena cava caudalis for assaying IS-5-MN.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 2-compartment model. The half-life for the distribution phase was about 6 min, for the elimination phase about 1.5 h. The latter was about 1/3 that obtained in man. From the comparison of the areas under the curve, a bioavailability of 71.5% was estimated. In a 2nd series of investigations, dogs were given 5 different doses of IS-5-MN orally (3.125-50 mg/dog). A rise in the peak plasma concentration occurred and the area under the curve was proportional to the dose, whereas the terminal half-life did not differ markedly. A close correlation was 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.

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