PMID: 3746630Feb 1, 1986Paper

Pharmacokinetics of isosorbide dinitrate and its mononitrate metabolites after intravenous infusion

Journal of Pharmacokinetics and Biopharmaceutics
Y SantoniY Frances

Abstract

Plasma concentrations of isosorbide dinitrate (ISDN) and its two active metabolites 2-isosorbide mononitrate (2-ISMN) and 5-isosorbide mononitrate (5-ISMN) have been measured during and for 6 hr after intravenous infusion at a rate of 2.5 mg/hr during 1.75 hr in six cardiac patients, by a capillary gas chromatographic method. Data were analyzed by simultaneous modeling of the observed kinetics of the three compounds. Two or three phases were detected on the postinfusion ISDN concentration-time curves. ISDN concentrations declined with a mean terminal half-life of 2.81 hr +/- 0.7 SD. The mean systemic clearance of ISDN (2.9 L/min +/- 0.7 SD) and its mean total volume of distribution (259 L +/- 48 SD) were relatively high. Plasma 5-ISMN concentrations were 5- to 6-fold greater than those of 2-ISMN during the whole observation period. Maximum levels of 2-ISMN (6.7 ng/ml +/- 0.9 SD) and of 5-ISMN (27 ng/ml +/- 6 SD) occurred within a few minutes after the end of infusion. The mean half-lives of 2-ISMN (1.59 hr +/- 0.19 SD) and of 5-ISMN (3.78 hr +/- 0.79 SD) estimated by the model were smaller than those calculated by a model-independent method (2.95 hr +/- 0.41 SD and 5.98 hr +/- 2.22, respectively), but were in good agreement wit...Continue Reading

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Citations

Jan 1, 1989·Annals of Biomedical Engineering·B B BaJ P Cano
Jun 27, 2008·European Journal of Clinical Investigation·A SchmidtE Buddecke

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