Long-acting, marked antiischemic effect maintained unattenuated during long-term interval treatment with once-daily isosorbide-5-mononitrate in sustained-release form.
In 18 patients with documented coronary artery disease, the antiischemic effect of 50 and 100 mg isosorbide-5-mononitrate (IS-5-MN) in sustained-release (SR) form was investigated using a randomized, double-blind, crossover, placebo-controlled protocol. After the initial administration of both dosages, compared to placebo there were significant reductions in exercise-induced ST-segment depression and significant increases in ischemia-free exercise time at all times of testing. At 12 hours, the 100-mg dosage still amounted to greater than 50% of its maximum and was significantly more marked than the 50 mg dose. Accordingly, the 100-mg dosage can be assumed to confer a longer duration of action. At the end of 3 weeks of long-term treatment, the significant antiischemic effects were not diminished versus those observed after initial administration. There was no evidence of tolerance development with either dosage. The IS-5-MN plasma concentration during long-term administration displayed, within the 24-hour treatment cycle, a clear decrease to low baseline values and a marked 5- to 7-fold increase after the daily dose in accordance with the response known to be prerequisite to successful interval treatment. Thus, the once-daily administration of IS-5-MN SR with dosages of 50 mg and, more markedly, 100 mg, provides effective antiischemic protection throughout the daily period of most physical activities in patients with stable angina pectoris.
Beyerle
A
A
German Heart Center Munich, Department of Cardiology, Federal Republic of Germany.
Reiniger
G
G
Rudolph
W
W
D001794:Blood Pressure / Q000187:drug effects; D003327:Coronary Disease / Q000188:drug therapy* / Q000503:physiopathology; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D004562:Electrocardiography / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007548:Isosorbide Dinitrate / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D005082:Physical Exertion; D016032:Randomized Controlled Trials as Topic; D013997:Time Factors
D003692:Delayed-Action Preparations; D007548:Isosorbide Dinitrate; C030397:isosorbide-5-mononitrate