BIOCHEMICAL-CHARACTERIZATION OF FLESTOLOL ESTERASE

The blood esterase that mediates the metabolism of flestolol, an ultra short-acting beta blocker, was characterized. Esterase activity occur red in plasma of human, dog, rat, and guinea pig and not in erythrocyt es of the same species. The esterase activity was greatest in humans a nd guinea pigs followed by dogs and rats. Purified human serum choline sterase was very active against flestolol while human serum albumin wa s slightly active. Human and bovine erythrocyte membrane acetylcholine sterases, electric eel acetylcholinesterase, human hemoglobin, dog, ra t, chicken, and bovine serum albumin were all inactive. Esterase activ ity with flestolol was inhibited in human, dog, and rat blood by echot hiophate, eserine, and sodium fluoride. Guinea pig blood esterase acti vity was inhibited by echothiopate and sodium fluoride, but not by ese rine. Metabolic interaction studies indicated that succinylcholine, pr ocaine, and chloroprocaine interfere with the metabolism of flestolol in human blood. Succinylcholine prolonged the in vitro half-life of fl estolol in dog blood, but acetylcholine, procaine, and chloroprocaine had no effect. Flestolol did not affect the metabolism of procaine or chloroprocaine in human and dog blood. The metabolism rate of flestolo l decreased in individuals with atypical, fluoride-resistant and silen t forms of serum cholinesterase.