Induction of cytochrome P-448 iso-enzymes and related glucuronyltransferases in the human liver by cigarette smoking

Human liver 10-20 mg from biopsy samples removed for diagnostic purposes from selected patients has been used for the preparation of microsomes. The activity of certain mono-oxygenases and UDP-glucuronyltransferases, as well as certain other enzymes involved in drug metabolism, has been determined using different substrates as indicators. Smokers oxidized benzo(a)pyrene and 7-ethoxyresorufin and also conjugated alpha-naphthol at a significantly increased rate compared to non-smokers. This indicates induction of certain mono-oxygenases and glucuronyltransferases which differs from the induction produced by phenobarbital. The findings can account for the reduced activity and increased elimination rate of certain drugs prescribed to smokers.