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Formation of the sulfone metabolite of di demethyl chlorpromazine in the rat in vivo and in vitro

Formation of the sulfone metabolite of di demethyl chlorpromazine in the rat in vivo and in vitro

Drug Metabolism & Disposition 7(6): 404-410

In peripheral tissues of male rats given 25 mg of didesmethylchlorpromazine [.gamma.-(2-chlorophenothiazinyl-10)-propylamine, Cl-PPA] per kg i.p. high levels of the corresponding sulfoxide (Cl-PPA-SO) and the sulfone (Cl-PPA-SO2) were measured during the following 2-24 h. 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, 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 induction and inhibition experiments did not lead to unequivocal conclusions concerning its nature.

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Accession: 005481609

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PMID: 43228

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