The widespread use of the phenothiazine tranquilizers in psychiatric treatment still confronts the clinician with unresolved problems in patient management. How, for example, does one determine the optimum dosage level for the individual patient? When maintenance drug therapy is discontinued, what accounts for the temporal patterns of relapse which so distinctly differentiate one patient from another? What biochemical processes underlie the commonly observed neurological complications of phenothiazine therapy? Clearly we must know the metabolic fate of these compounds before such questions can be definitively answered.
Although a number of studies have found differential metabolic patterns for the phenothiazines in animals, little is known of their metabolism in man. This led us to determine amount of unchanged chlorpromazine excreted in urine of schizophrenic patients.1 The quantity was found to be usually less than 1% of the administered dose. In that investigation three chlorpromazine