The pharmacokinetics and pharmacodynamics of
flestolol, a new short-acting,
beta-adrenergic receptor antagonist, were examined in nine healthy subjects after a constant
intravenous infusion of 5 micrograms/kg/min for 72 hours.
Flestolol blood levels were determined by high-performance liquid chromatography. In all subjects,
flestolol blood concentration attained steady state 30 minutes after initiation of infusion. The mean +/- standard deviation steady-state concentration of
flestolol was 31.1 +/- 12.0 ng/mL. The elimination half-life averaged 7.2 minutes. The mean +/- standard deviation total body clearance was 181 +/- 66 mL/min/kg. The apparent volume of distribution and the area under the curve averaged 1.89 L/kg and 2.23 micrograms-hr/mL, respectively.
Flestolol did not cause any significant change (P greater than .05) in the heart rate or systolic or diastolic blood pressure from the baseline.
Flestolol significantly (P less than .05) attenuated the
isoproterenol-induced increase in heart rate and systolic blood pressure and decrease in diastolic blood pressure in comparison with baseline. The average maximum reduction in
isoproterenol tachycardia was in the range of 63% to 79% during
flestolol infusion. There was a rapid recovery from beta blockade after termination of
flestolol infusion; the recovery averaged 96% 20 minutes after the infusion was stopped. We conclude that
flestolol exhibits a very short half-life and is cleared mainly by extrahepatic routes. It is an effective beta blocker and possesses a short duration of action.