Abstract

The distribution of radioactivity, metabolic degradation and mode of action of C¹⁴-fluphenazine enanthate (FE) were studied in the rat. Following a single subcutaneous injection of 30 mg of FE per kg as a solution in sesame oil radioactivity was found to have been widely distributed, but the major portion was found in the carcass. The brains contained the least amount of the drug of any of the organs studied. The concentrations decreased from 0.2% of the dose immediately after the injection to 0.04% 21 days later. This amount of drug was sufficient to produce a tranquilizing effect for a 3-week period. A sizable quantity of the dose was found throughout the rat in the form of a nonextractable, nonidentified fraction. In addition to Unchanged FE, 2 metabolites, fluphenazine (F) and fluphenazine sulfoxide (FSO) were identified in the excreta and all the tissues studied except brain. F was the only compound identified in the brain after the injection of either FE or F. The hydrolysis in the brain of FE to F was demonstrated. Radioactivity was excreted in the feces and urine over an extended period.

The experiments support the view that subcutaneously injected FE in oil acted for a prolonged period because the multiple depot sites that had been formed released slowly the active agents, F or FE. Evidence has been presented that the active agent ultimately deposited in the brain was F.