Hemodynamic Effects of Flestolol, a Titratable Short‐Acting Intravenous Beta‐Adrenergic Receptor Blocker

Abstract

The hemodynamic effects of flestolol were evaluated in 30 patients undergoing routine cardiac catheterization. Hemodynamic measurements were obtained during baseline (prior to flestolol), at steady state during IV flestolol infusion (1, 5, and 10 micrograms/kg/min) and at 20 to 30 minutes after discontinuation (postinfusion). Flestolol-induced hemodynamic changes were similar to those induced by other beta blockers without intrinsic sympathomimetic activity. Significant dose-dependent reduction in heart rate, rate pressure product, and increase in peripheral vascular resistance were seen. Flestolol produced clinically insignificant decrease in myocardial contractility as shown by slight decrease in LVdp/dt, CI, and LVEF. Hemodynamic data from patients with paced heart rate, further confirms a direct mild cardiac depressant effect of flestolol, a finding common to other beta blockers. Consistent with the short elimination half-life of flestolol (t1/2 = 6.5 minutes), most of the hemodynamic changes rapidly returned to preinfusion level within 20 to 30 minutes following its discontinuation. Thus flestolol, with its unique pharmacokinetic profile and titrability, may be beneficial in the treatment of critically ill patients.

Retrometabolism‐Based Drug Design and Targeting

“…Flestolol (20, ACC-9089) a compound with such a 2-F substituent was selected for further toxicological evaluation and clinical study. All clinical findings were consistent with the SD hypothesis: flestolol was safe and effective, had a short elimination half-life of approximately 7 min and, thus, a rapid recovery from b-block after termination of infusion, and was cleared mainly by extrahepatic routes [131,132]. Interestingly, an investigation of the metabolism of flestolol and other esters found polymorphic rates of ester hydrolysis in New Zealand white rabbit blood and cornea [90].…”