PMID: 43228Nov 1, 1979

Formation of the sulfone metabolite of didesmethylchlorpromazine in the rat in vivo and in vitro

Drug Metabolism and Disposition : the Biological Fate of Chemicals
H Kreft, U Breyer-Pfaff

Abstract

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.

Related Concepts

Lung
Brain
Sulfoxides
Kidney
Thorazine
Biliary Sludge
Sulfones
Liver

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