Tolerance and beta‐adrenergic blocking activity of flestolol, a short‐acting beta blocker

The tolerance and β‐adrenergic blocking activity of flestolol, a short‐acting β‐blocker, was investigated in 30 subjects. Flestolol infused intravenously at doses up to 100 μg/kg/min was found to be well tolerated. A dose‐dependent attenuation of isoproterenol‐induced tachycardia and increase in systolic blood pressure occurred with flestolol at doses ranging from 0.5 to 15.0 μg/kg/min. The average percent reduction in isoproterenol‐induced tachycardia (β‐blockade) at each dose of flestolol, 0.5, 2.5, 5.0, 15.0, and 50.0 μg/ kg/min, was 15.1%, 45.9%, 67.0%, 85.9%, and 90.3%, respectively. The onset of β‐blockade occurred within 30 minutes. After the end of flestolol infusion there was a marked reduction in β‐blockade within 6 minutes, with complete recovery from β‐blockade within 30 to 45 minutes. There was a statistically significant (P < 0.01) positive correlation between flestolol dosage and its blood levels (r = 0.91) as well as between the flestolol‐induced β‐blockade and its dosage (r = 0.62). Clinical Pharmacology and Therapeutics (1986) 39, 543–549; doi: 10.1038/clpt.1986.93