Usefulness of twice-daily isosorbide-5-mononitrate in preventing development of tolerance in angina pectoris

Abstract Development of tolerance to nitrates during long-term therapy is a major concern. It has been suggested that isosorbide-5-mononitrate (IS-5MN), an active metabolite of isosorbide dinitrate, administered twice daily 12 hours apart does not lead to development of tolerance. The duration of effects of IS-5MN at a dose of 20 and 40 mg and of placebo was studied in patients with angina pectoris who responded to nitrates after the first dose (n = 12) and after 1 week of twice-daily therapy (n = 9). The study was double-blind, randomized and crossover in design. Compared with placebo values, after the first dose of 20 and 40 mg IS-5MN, exercise duration was higher at 2 hours (p