The biotransformation of thioridazine to thioridazine 5-sulfoxide stereoisomers in phenobarbital induced rats.

The disposition and urinary elimination of thioridazine 5-sulfoxide (ring sulfoxide) following subacute administration of thioridazine was investigated in control and phenobarbital (Pb) induced rats. The ring sulfoxide exists as two stereoisomeric pairs, identified by high performance liquid chromatography as fast eluting (RSF) and slow eluting (RSS) ring sulfoxide. No major differences were detected in the distribution in serum or tissue of the ring sulfoxide between control and induced animals. The ring sulfoxide accumulated in all tissues studied. RSF tissue concentrations were significantly greater than those of RSS in both groups. However, stereoselective formation and elimination of the two ring sulfoxides was not noted in either group. Pb inducible cytochrome P-450 drug metabolizing enzymes do not appear to play a major role in the biotransformation of thioridazine to the ring sulfoxide.