Effect of oral administration of methadone on hepatic microsomal mixed function oxidase activity in mice

Daily oral administration of methadone (50 mg/kg) brought about a 2-fold increase in the activity of liver N-demethylase in mice within a few days and maintained this high level of activity for the 30-day duration of the experiment. An increase in hepatic microsomal protein and a decrease in pentobarbital sleeping times were noted in the methadone-treated animals. Subcutaneous administration of methadone (20 mg/kg) for 6 days resulted in a much smaller increase in the activity of N-demethylase.