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.
German Heart Center Munich, Department of Cardiology, Federal Republic of Germany.
A
A
Beyerle
G
G
Reiniger
W
W
Rudolph
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