title: Effects of 8:00 a.m. and 2:00 p.m. doses of isosorbide-5-mononitrate during twice-daily therapy in stable angina pectoris.
abstract: "Trough" plasma concentrations of isosorbide-5-mononitrate (IS-5-MN), an active metabolite of isosorbide dinitrate, of less than 95 ng/ml are considered necessary to prevent development of tolerance to isosorbide dinitrate and IS-5-MN. In a double-blind, crossover, placebo-controlled study, the effects of IS-5-MN during twice daily eccentric therapy were evaluated in 18 patients with reproducible exercise-induced angina who were nitrate responders. In a random order, patients received either placebo or IS-5-MN (20 mg) at 8 a.m. and 2 p.m. for 1 week each. Average trough plasma IS-5-MN concentrations before the 8 a.m. and 2 p.m. doses were 67 and 226 ng/ml, respectively, and increased to 382 and 488 ng/ml 2 hours after the 8 a.m. and 2 p.m. doses, respectively. Despite a more than threefold higher trough plasma IS-5-MN concentration before the 2 p.m. dose than before the 8 a.m. dose, the increase in exercise duration 2 hours after the doses was similar (1.21 minutes [21%] after 8 a.m. dose, and 1.08 minutes [19%] after 2 p.m. dose). These increases in exercise duration after IS-5-MN were significantly (p less than 0.01) greater than those observed after placebo (0.17 minutes [3%] after 8 a.m. dose, and -0.05 minute [-0.5%] after 2 p.m. dose). Reduction in standing systolic blood pressure at 2 hours after the doses was also nearly identical after the 8 a.m. and 2 p.m. doses of IS-5-MN (21 [15%] and 19 [14%] mm Hg, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City 73190.
authors.forename: U
authors.initials: U
authors.lastname: Thadani
authors.forename: N
authors.initials: N
authors.lastname: Bittar
mesh_terms: D000368:Aged; D000787:Angina Pectoris / Q000188:drug therapy* / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004562:Electrocardiography; D005080:Exercise Test; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007548:Isosorbide Dinitrate / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D014665:Vasodilator Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics
chemical_list: D014665:Vasodilator Agents; D007548:Isosorbide Dinitrate; C030397:isosorbide-5-mononitrate