RAPID INVITRO SULFOXIDATION OF CHLORPROMAZINE BY HUMAN-BLOOD - INHIBITION BY AN ENDOGENOUS PLASMA-PROTEIN FACTOR

Sulfoxidation of chlorpromazine is a major metabolic pathway in humans and is clinically significant insofar as chlorpromazine-sulfoxide is thought to be pharmacologically inactive. Sulfoxidizing capacities of hepatic and extrahepatic tissues were examined in vitro. Liver, lung, and gut, but not brain, were found to have differential activities (liver>lung>gut) which were NADPH dependent and had characteristics of enzymatic reactions. NADPH independent sulfoxidation of chlorpromazine is seen in the presence of whole blood. This reaction reaches completion in less than 5 sec. and is considerably more active than that seen with other tissues; the total sulfoxidizing capacity of whole blood can be attributed to hemoglobin. Plasma contains a protein-like factor that actively inhibits blood-catalyzed chlorpromazine sulfoxidation. This factor has a molecular weight of 72,000±6000 daltons. The possible roles of this protein in regulating phenothiazine metabolism are discussed. © 1979.