[Acute and subchronic effect of a patch with discontinuous nitroglycerin liberation]

We investigated a new patch with 15 mg nitroglycerine and a drug release of 70% during the first 12 h of application, designed to prevent tolerance. In a double blind placebo controlled trial 12 patients with angiographically significant coronary artery disease, angina and reproducible ST-segment depression during exercise were studied. Stress-tests with a constant workload were performed before, 1 h, 4 h and 8 h after first day application as well as after 8-10 days of therapy. At the first day the sum of ST-segment depression (lead V 5) during each minute of exercise and the 5 minutes of recovery decreased by 55.5% (1 h, p less than 0.001), 47.4% (4 h, p less than 0.001) and 28.4% (8 h, n.s.). After subchronical application the relative values were 32% (1 h, p less than 0.05), 23.8% (4 h, n.s.) and no change after 8 h. Thus the new patch is effective between 1 h and 8 h of acute application. With chronic therapy however tolerance occurs despite the fact that only a small amount of nitroglycerine is released during the last half of a 24 h application.