POLYMORPHIC METABOLISM OF FLESTOLOL AND OTHER ESTER-CONTAINING COMPOUNDS BY A CARBOXYLESTERASE IN NEW-ZEALAND WHITE-RABBIT BLOOD AND CORNEA

Flestolol, thyl)-2-hydroxy-3-(o-fluorobenzoytoxy)propylamine, (F), is an ester containing an ultra short-acting beta blocker intended for th e treatment of myocardial dysfunctions. In vitro incubation of F, proc aine, chloroprocaine, and atropine with blood from different New Zeala nd White (NZW) rabbits resulted in a bimodal distribution (70% fast, 3 0% slow) of ester hydrolysis rates. Using F as a model substrate, bimo dal hydrolysis rates were also observed in NZW rabbit cornea but not a queous humor, iris-ciliary body complex and ocular tissues of pigmente d rabbits. In addition, the bimodal distribution of esterase activity was not observed in blood from rats, dogs, and humans. Incubation of e sters at various positions of the phenoxypropanolamine nucleus of beta blockers with NZW rabbit blood indicated structural specificity of th e carboxylesterase in terms of unimodal or biomodal distribution of ac tivity. These results strongly suggest that the carboxylesterase in NZ W rabbit blood that hydrolyzes F and similar compounds is atropine est erase as described in the literature.