title: Eccentric dosing with isosorbide-5-mononitrate in angina pectoris.
abstract: In a placebo-controlled, parallel, double-blind study, 214 patients with stable angina were studied. Doses of 5, 10 and 20 mg of immediate-release isosorbide-5-mononitrate (IS-5-MN) or placebo were administered at 0800 and 1500 hours for a period of 3 weeks. On days 1 and 14, patients underwent exercise testing before, and 2 and 7 hours after both doses; on days 7 and 21, testing was performed 2 hours after morning dosing. Study variables included total exercise duration and time to moderate angina. On day 1, the active treatment groups showed improvement over the placebo group 2 and 7 hours after dose 1, and 2 hours after dose 2. Throughout the subsequent study period, each active treatment group was superior to placebo 2 hours after the first and second doses. Only the 20 mg dose increased exercise duration 7 hours after dosing, and this was observed after both doses 1 and 2 on day 14. There were fewer episodes of angina in patients receiving the 20 mg dose. There was no increase in nocturnal angina during eccentric dosing with IS-5-MN. In comparing exercise times throughout the study, tolerance did not develop during eccentric dosing. The morning exercise tests before tablet administration showed a progressive increase during the study period, with slightly greater improvement in patients receiving active therapy. This absence of a zero hour effect suggests that rebound does not occur during eccentric dosing with immediate-release IS-5-MN.
authors.affiliation: Department of Medicine, Queen's University, Kingston General Hospital, Ontario, Canada.
authors.forename: J O
authors.initials: JO
authors.lastname: Parker
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000787:Angina Pectoris / Q000188:drug therapy* / Q000503:physiopathology; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004361:Drug Tolerance; D004562:Electrocardiography; D005080:Exercise Test; D005260:Female; D006801:Humans; D007548:Isosorbide Dinitrate / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000188:drug therapy / Q000503:physiopathology; D010919:Placebos; D013607:Tablets; D013997:Time Factors; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D010919:Placebos; D013607:Tablets; D014665:Vasodilator Agents; D007548:Isosorbide Dinitrate; C030397:isosorbide-5-mononitrate