The kinetics of hydrolysis of the carbamoyl group in salicylanilide N-methylcarbamate (I) and 4-biphenylyl N-methylcarbamate (11) showed that the reaction was first order with respect to both hydroxide ion and carbamate. At 37", the hydroxideion-catalyzed hydrolysis of 1 to yield salicylanilide (111) proceeded at a rate over 200 times that for the hydrolysis of I1 to produce 4-biphenyl01 (IV). Half-lives of I and I1 at pH 7.3 were 11 min. and 38.2 hr., respectively. Following oral administration of I to human subjects, only conjugated 111, corresponding to 10% of the dose, was detected in urine. In the case of 11, urinary excretion products were I1 (0.4OX), IV (l.l4X), and conjugated IV (4Ox). Taken together, these results are consistent with extensive, if not complete, hydrolysis of I in the intestine to yield relatively poorly absorbed 111 compared to a considerably more efficient absorption of the neutral Compound I1 followed by its nearly complete hydrolysis and conjugation.
Keyphrases
Salicylanilide N-methylcarbamate-hydrolysis, i)I uitro kinetics, in uiao urinary excretion, metabolites 0 CBiphenylyl N-methylcarbamate-hydrolysis, in uitro kinetics, in uiuo urinary excretion, metabolites 0 Urinary excretion-hydrolysis of salicylanilide and 4-biphenylyl N-methylcarbamates, metabolites Hydrolysis, in uitro, in uiuo-salicylanilide and 4-biphenylyl N-methylcarbamates