Sustained effect of and lack of development of tolerance to controlled-release isosorbide-5-mononitrate in chronic stable angina pectoris.
Tolerance has been shown to develop when nitrate preparations are used in such a manner as to produce plasma levels within the therapeutic range continuously over a 24-hour period. However, a period of reduced or low nitrate plasma levels of a few hours per day may limit or completely prevent tolerance development. In 18 patients with chronic stable angina pectoris, a single 60-mg daily dose of a controlled-release preparation of isosorbide-5-mononitrate (ISMN) was compared with the administration of 30 mg, 4 times daily, of immediate-release isosorbide dinitrate (ISDN) in a double-blind, randomized, placebo-controlled, crossover study. The comparisons were carried out on the first day of therapy and after 11 to 14 days of continuous therapy to assess the duration of effectiveness and the development of tolerance. On short-term therapy, both drugs produced a significant improvement in treadmill walking times to moderate angina in comparison with placebo. The values for ISMN were 87 +/- 99 seconds (23%) at 12:30 P.M., 72 +/- 91 seconds (19%) at 5 P.M. and 51 +/- 81 seconds (13%) at 8:30 P.M. For ISDN, the respective values were 71 +/- 83 seconds (19%), 89 +/- 98 seconds (24%) and 79 +/- 87 seconds (21%). There were no significant differences between drugs. Plasma nitrate levels for each drug paralleled the improvements in exercise performance.(ABSTRACT TRUNCATED AT 250 WORDS)