PT  - JOURNAL ARTICLE
AU  - H Kreft
AU  - U Breyer-Pfaff
TI  - Formation of the sulfone metabolite of didesmethylchlorpromazine in the rat in vivo and in vitro.
DP  - 1979 Nov 01
TA  - Drug Metabolism and Disposition
PG  - 404--410
VI  - 7
IP  - 6
4099  - http://dmd.aspetjournals.org/content/7/6/404.short
4100  - http://dmd.aspetjournals.org/content/7/6/404.full
SO  - Drug Metab Dispos1979 Nov 01; 7
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.