Biotransformation of Morphinone and Its Glutathione Adduct Derived from Morphine by Anaerobic Gut Microbes in Guinea Pigs

Abstract

Morphinone (MO) and its glutathione adduct (MO-GSH) are excreted into bile of guinea pigs after subcutaneous administration of morphine (M). In the present study, we examined metabolites of M in guinea pig feces. Surprisingly, minimal amounts of MO and MO-GSH were excreted into the feces, whereas dihydromorphine (DHM) and dihydromorphinone (DHMO), which are not found in bile of guinea pigs administered M, were detected in the feces. Incubation of MO and MO-GSH with the contents of the large intestine under anaerobic conditions resulted in their conversion into DHMO. These results suggest that MO-GSH undergoes C–S cleavage by gut microbes to form MO, which is anaerobically reduced to DHMO excreted into feces.