RT Journal Article SR Electronic T1 Formation of the sulfone metabolite of didesmethylchlorpromazine in the rat in vivo and in vitro. JF Drug Metabolism and Disposition JO Drug Metab Dispos FD American Society for Pharmacology and Experimental Therapeutics SP 404 OP 410 VO 7 IS 6 A1 H Kreft A1 U Breyer-Pfaff YR 1979 UL http://dmd.aspetjournals.org/content/7/6/404.abstract AB In peripheral tissues of male rats given 25 mg of didesmethylchlorpromazine [gamma-(2-chlorophenothiazinyl-10)-propylamine, Cl-PPA] per kg ip, high levels of the corresponding sulfoxide (Cl-PPA-SO) and the sulfone (Cl-PPA-SO2) were measured during the following 2-24 hr. Small quantities of these metabolites were excreted in bile, whereas 7-hydroxy-Cl-PPA could not be detected. By comparison of the areas under the tissue concentration-time curves with those measured after injection of Cl-PPA-SO2, it could be shown that at least 50% of the Cl-PPA dose was converted to the sulfone. Following administration of Cl-PPA-SO, the sulfone was present in tissues and in urine. An NADPH-dependent oxygenase catalyzing the conversion of Cl-PPA-SO to Cl-PPA-SO2 was localized in liver microsomes. Attempts to characterize the enzyme by means of induction and inhbition experiments did not lead to unequivocal conclusions concerning its nature.