[Lack of tolerance development in interval therapy with 50 mg isosorbide-5-nitrate retard (Elantan long)]

Fluctuating mononitrate plasma levels in the course of 24 h are a prerequisite for prevention of nitrate tolerance in patients with angina pectoris undergoing longterm treatment. In 12 patients with angiographically proven coronary artery disease (54 +/- 7 years) effects of 50 mg Isosorbide-5-mononitrate (IS-5-MN) in a slow-release (SR) formulation on hemodynamics and exercise tolerance were evaluated after a first dose and at the end of a 1-week treatment period with 50 mg given once-daily. 1 and 2 h after medication mean pulmonary artery pressure (PAP) at rest was reduced by 30% (p less than 0.001) and 25% (p less than 0.01 respectively. During submaximal bicycle exercise (50 W, 3 min) PAP was significantly reduced by IS-5-MN by 35% (1 and 2 h after medication). At the end of exercise (discontinuation), drug-induced reductions of PAP were 19% (1 h) and 21% (2 h) (p less than 0.05), respectively. IS-5-MN led to a marked increase of exercise capacity (base-line: 396 +/- 119 W x min); 1 h: 646 +/- 153 W x min (p less than 0.01). At stress testing 2, 4 and 10 h post medication improvements were 67% (p less than 0.01), 49% (p less than 0.01) and 28% (p less than 0.01), respectively. 24 h after medication baseline values were reached again. After a 1-week treatment with 50 mg IS-5-MN SR daily, beneficial effects of the drug on hemodynamics and working capacity could be demonstrated. Again, significant effects could be shown up to 10 h after drug administration. Thus, IS-5-MN SR administered once daily proved effective in intermediate-term treatment of patients with coronary artery disease with regard to hemodynamics and exercise capacity.(ABSTRACT TRUNCATED AT 250 WORDS)