title: Pharmacokinetics of isosorbide-5-mononitrate after oral administration of an extended-release mononitrate formulation versus a standard dinitrate formulation.
abstract: The steady-state pharmacokinetic profile of isosorbide-5-mononitrate (5-ISMN) after oral administration of an extended-release tablet formulation of 5-ISMN 60 mg or 120 mg once a day was compared with that after administration of isosorbide dinitrate (ISDN) 40 mg every 6 hours, in a randomized, open-label, three-way crossover trial in 24 healthy men. After oral administration of extended-release 5-ISMN 60 mg or 120 mg once daily, 5-ISMN was slowly absorbed, reaching mean peak plasma concentrations of 557 and 1151 ng/mL, respectively, in approximately 3 hours. Plasma concentrations of 5-ISMN were dose proportional between 60 mg and 120 mg. After oral administration of ISDN 40 mg every 6 hours, a mean peak plasma 5-ISMN concentration of 806 ng/mL was achieved in less than 2 hours (mean time to reach the maximum plasma concentration was 1.5 hours). The mean plasma apparent elimination half-life of 5-ISMN was 6.2 hours after extended-release 5-ISMN administration and 7.1 hours after ISDN. Although the maximum plasma concentration was higher and the minimum plasma concentration was lower after administration of extended-release 5-ISMN 120 mg once daily compared with ISDN 40 mg every 6 hours, there was no significant difference (P > 0.05) in the "bioavailability" of 5-ISMN between these two treatments. The most commonly reported adverse events in these "nitrate-naive" subjects were headache, dizziness, nausea, and vomiting; these were dose related and their incidence decreased with repeated exposure.
authors.affiliation: Department of Clinical Pharmacology, Schering-Plough Research Institute, Schering-Plough Corporation, Kenilworth, New Jersey, USA.
authors.forename: T
authors.initials: T
authors.lastname: Kosoglou
authors.forename: J E
authors.initials: JE
authors.lastname: Patrick
authors.forename: A
authors.initials: A
authors.lastname: Cohen
authors.forename: E
authors.initials: E
authors.lastname: Radwanski
authors.forename: D
authors.initials: D
authors.lastname: Christopher
authors.forename: M B
authors.initials: MB
authors.lastname: Affrime
mesh_terms: D000284:Administration, Oral; D000328:Adult; D001682:Biological Availability; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004334:Drug Administration Schedule; D006207:Half-Life; D006801:Humans; D007548:Isosorbide Dinitrate / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D014665:Vasodilator Agents / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D003692:Delayed-Action Preparations; D014665:Vasodilator Agents; D007548:Isosorbide Dinitrate; C030397:isosorbide-5-mononitrate