Mutual Inhibition in Hydroxylation of Acetanilide and N-Phenylurea in Rabbits

Blood concentration of unchanged N-phenylurea and the urinary excreted amount of its metabolites were determined periodically, after intravenous administration of N-phenylurea. Blood concentration time course of N-pheylurea observed was well explained by a pharmacokinetic model that assumes Michaelis Menten equation for hydroxylation step and a first order process for the metabolism of N-phenylurea other than hydroxylation. This result is analogous to that of acetanilide reported previously. In addition, elimination rate of acetanilide from the blood was affected and reduced by the simultaneous administration of N-phenylurea. It was proved that the hydroxylation process of these drugs was mutually inhibited. Computation of the theoretical values were carried out by means of an analog computer.