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For the purpose of determining exercise intensity required for evaluating the effect of beta-blocking agents, the multi-stage treadmill exercise was carried out up to intensity of 85% of maximal oxygen intake (VO2max) after administration of beta-blocking agents in 7 healthy men. To obtain a stable dose response in the inhibitory effect of beta-blocking agents on heart rate (HR) and systolic blood pressure (S-BP), the exercise intensity more than 65% of VO2max (75% of maximal heart rate) was needed. In order to evaluate the effect of befunolol (BFE), a submaximal treadmill exercise of 75% of the age adjusted predicted maximal heart rate was loaded in 6 healthy men at 1.5, 4, and 8 hours following a single oral administration of 10 mg, 20 mg or 40 mg of BFE and 20 mg or 40 mg of propranolol. Simultaneously, the plasma concentration of BFE was determined 1.5, 4, 6 and 8 hours after the administration of BFE at each dose. In human serum, BFE was detected together with its metabolite, revealing a significant correlation between BFE and metabolite (r = 0.94, p &lt; 0.001). Almost a certain rate of metabolite (4--5 times) was detected against BFE. As for the biological half life, it was 1.79 +/- 0.13 hours with BFE and 3.67 +/- 1.33 hours with metabolite. The inhibitory effect of BFE on HR and S-BP during exercise exhibited a dose response with the oral dose and its plasma concentration, and was almost twice as much as that of propranolol at the same dose. Accordingly, the myocardial oxygen consumption which may be represented as rate pressure product was inhibited twice as much as propranolol. BFE is characteristic of its more rapid elimination of its effect compared to the other beta-blocking agents. The decrease in the inhibitory effect of BFE or HR during exercise was about 1.8 times quicker than that of propranolol.

Effects of oral befunolol on heart rate and systolic blood pressure during submaximal exercise in man.