Dose-effect relationship amongst three different sustained-release forms of isosorbide 5-mononitrate in patients with...

Fifteen patients with coronary artery disease and stable angina pectoris were included in a double-blind, randomized, cross-over study. The patients received 25, 50 and 100 mg isosorbide 5-mononitrate, as well as a placebo, for subsequent 1-week periods. On the 7th day of each treatment period, 8 h after medication application, an exercise test was performed. A highly significant (p less than 0.001) and dose-dependent reduction of the sum of the ST-segment depression was observed at similar workloads: 28.6, 46 and 63.5% decreases occurred at the 25, 50 and 100 mg isosorbide 5-mononitrate doses, respectively. Compared to placebo, the frequency of anginal attacks and the consumption of nitroglycerin likewise decreased highly significantly (p less than 0.001) with all three doses. Isosorbide 5-mononitrate plasma levels (8 h post-application) increased linearly with the dose; amounting to 228 +/- 53, 485 +/- 93 and 991 +/- 177 ng/ml at the 25, 50 and 100 mg doses of the sustained release medication forms, respectively.