Effects of 8:00 a.m. and 2:00 p.m. doses of isosorbide-5-mononitrate during twice-daily therapy in stable angina pectoris.

"Trough" plasma concentrations of isosorbide-5-mononitrate (IS-5-MN), an active metabolite of isosorbide dinitrate, of less than 95 ng/ml are considered necessary to prevent development of tolerance to isosorbide dinitrate and IS-5-MN. In a double-blind, crossover, placebo-controlled study, the effects of IS-5-MN during twice daily eccentric therapy were evaluated in 18 patients with reproducible exercise-induced angina who were nitrate responders. In a random order, patients received either placebo or IS-5-MN (20 mg) at 8 a.m. and 2 p.m. for 1 week each. Average trough plasma IS-5-MN concentrations before the 8 a.m. and 2 p.m. doses were 67 and 226 ng/ml, respectively, and increased to 382 and 488 ng/ml 2 hours after the 8 a.m. and 2 p.m. doses, respectively. Despite a more than threefold higher trough plasma IS-5-MN concentration before the 2 p.m. dose than before the 8 a.m. dose, the increase in exercise duration 2 hours after the doses was similar (1.21 minutes [21%] after 8 a.m. dose, and 1.08 minutes [19%] after 2 p.m. dose). These increases in exercise duration after IS-5-MN were significantly (p less than 0.01) greater than those observed after placebo (0.17 minutes [3%] after 8 a.m. dose, and -0.05 minute [-0.5%] after 2 p.m. dose). Reduction in standing systolic blood pressure at 2 hours after the doses was also nearly identical after the 8 a.m. and 2 p.m. doses of IS-5-MN (21 [15%] and 19 [14%] mm Hg, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

RCT Entities:   Population Interventions Outcomes