Studies on the microsomal formation of arylating metabolites of acetaminophen and phenacetin.

摘要: A chemically reactive metabolite of phenacetin is formed by a cytochrome P-450 in hamster liver microsomes mechanism that different from the generation acetaminophen. The V max covalent binding exceeds acetaminophen, showing not first deethylated to which then activated. Previous treatment with 3-methylcholanthrene increases for acetaminophen but decreases phenacetin, even though it deethylation phenobarbital without increasing same parameter Addition sodium fluoride (0.1 M) rate phenacetin. When prevented trapping metabolites glutathione during incubations carried out under 18O2 atmospheres, reductive cleavage Raney nickel conjugates either or yields acetaminophen; however, phenacetin-glutathione contains about 50% 18O position 4, whereas acetaminophen-glutathione virtually no 18O. These findings are consistent hypothesis converted N -hydroxyacetaminophen, dehydrates yield arylating species, acetimidoquinone, species arises epoxidation.