Pharmacokinetic approach of plafibride in rat

The serum concentration of N-2-(p-chlorophenoxy)-isobutyryl-N'-morpholinomethylurea (plafibride, ITA 104) and its metabolites was measured in the rat after oral and intravenous administration of the drug. Plafibride was distributed in the rat according to an open two-compartment model. Moreover, 2-(p-chlorophenoxy)isobutyrylurea and clofibric acid were detected. In the urine, 81.7% of the administered dose was recovered in the form of free clofibric acid, 0.8% as plafibride itself and 1.1% as 2-(p-chlorophenoxy)isobutyrylurea. The amount of plafibride and its metabolites present in the feces was practically negligible. A mechanistic scheme for the degradation of plafibride is proposed, which agrees with the observed pharmacological and pharmacokinetic data.