In order to investigate the effect of isosorbide 5mononitrate (5-ISMN) on exercise tolerance, a controlled study was carried out in 11 patients with effort angina pectoris. Multistage treadmill exercise testing was performed before, and 2, 4, and 7 hours after a single oral dose of placebo at 9: 30 to 10 o'clock in the morning. Two to seven days later, the test was again performed with the test drug (TY-10368) containing 20 mg of 5-ISMN according to the identical test protocol. It was terminated at moderate anginal pain.
Before administration, there were no significant differences in treadmill exercise duration, pressure-rate product (PRP), and ST deviation between TY-10368 and placebo.
At 2, 4, and 7 hours after the administration, the exercise duration was significantly longer after TY-10368 than after placebo (P<0.01).
At 2 hours after the administration, peak PRP was significantly greater after TY-10368 than after placebo (P<0.05). ST deviation at peak exercise showed no significant difference between TY-10368 and placebo. PRP and ST deviation at the same exercise time were significantly smaller or tended to be smaller after TY-10368 than placebo.
There was a significant linear correlation between plasma 5-ISMN concentration and Δ ExD (exercise duration after administration minus that before administration) (r=0.42, P<0.05).
At 7 hours after a single oral administration of TY-10368, the mean plasma level of 5-ISMN was sustained above 200 ng/ml, which was regarded as the minimum effective plasma concentration of the compound for effort angina in the present study.
These results showed that TY-10368 significantly increased exercise tolerance in patients with effort angina pectoris even at 7 hours after a single oral dose, and was considered to be a clinically useful oral antianginal agent.
