PMID: 9549637Apr 29, 1998Paper

Pharmacokinetics of isosorbide dinitrate in healthy volunteers after 24-hour intravenous infusion

Journal of Clinical Pharmacology
A BergamiR Latini

Abstract

No studies have examined the pharmacokinetics of isosorbide dinitrate (ISDN) after infusion of long duration, even though such infusions are used in patients. We therefore measured ISDN and its active metabolites, isosorbide-5-mononitrate (IS5MN) and isosorbide-2-mononitrate (IS2MN), in plasma of 9 healthy volunteers who received a continuous intravenous infusion of ISDN for 24 hours at a dose rate that lowered diastolic blood pressure by 10% during the first 30 minutes of infusion. All subjects tolerated the infusion except one who experienced intolerable headache. Five subjects received 1 microgram.min-1.kg-1, one 2 micrograms.min-1.kg-1, and two 4 micrograms.min-1.kg-1 ISDN, whereas the full rate of 6 micrograms.min-1.kg-1 was used continuously in one subject. At all infusion rates the plasma concentrations of ISDN were higher at 24 hours than at earlier times, suggesting that a steady-state condition had not been reached at that time. The same was true for the mononitrate metabolites, which reached higher plasma concentrations and were cleared more slowly than the parent compound after the end of the infusion. Apparent elimination half-lives of ISDN, IS2MN, and IS5MN were 67 +/- 10 minutes, 115 +/- 13 minutes, and 272 +/- 3...Continue Reading

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