Hydrolysis of 4-Acetamidophenyl 2,2,2-Trichloroethyl Carbonate by Esterolytic Enzymes from Various Sources

Hydrolysis rates were determined for ATC in pH 7.4 phosphate buffer containing human plasma from a number of individuals; human plasma treated and stored in various ways; several Cohn fractions of human plasma; human plasma treated with various esterase inhibitors; and a number of commercially available enzymes. The variation among individual plasma samples was observed, as well as the way in which blood type, plasma concentration, lyophilization, freezing, thawing, storing the plasma at 25°, ethanol concentration, and substrate concentration influenced the catalytic potency of human plasma. Studies with the Cohn fractions and esterase inhibitors suggested that pseudocholinesterase was primarily responsible for the enzymatic activity of human plasma with respect to ATC hydrolysis. Some proteolytic enzymes were also found to be potent catalysts of ATC hydrolysis. It was concluded that, following oral administration, ATC would be exposed to many enzymes that are potent catalysts for its hydrolysis, both in the gastrointestinal tract and following absorption and distribution in body tissue.