Stereoselective debromination of R, S-(α-bromoisovaleryl)urea (R, S-BIU) to isovalerylurea (IVU) in rats in vivo and in vitro was shown. IVU was isolated and identified in the blood of rats dosed R, S-BIU. When S- or R-BIU was intraperitoneally dosed to rats, the amounts of IVU from S-BIU was higher than that from R-enantiomer. The amounts of IVU from S-BIU was enhanced by the pretreatment of rats with phenobarbital. The debromination of BIU by rat liver slices showed the similar stereoselective debromination and was stimulated by the pretreatment of rats with phenobarbital. In contrast, the stereoselective debromination of BIU by rat blood and rat cecum contents was not observed. Human liver microsomes exhibited the debrominating activity, but the activity was markedly varied among samples. When the debromination activity was examined using recombinant CYPs expressed human CYPs in human B limphoblastoid cells, CYP2A6 exhibited the highest activity, and followed by CYP2B6, 2D6 and 3A4. In these cases, the stereoselective debromination toward S-BIU was also observed.
