Lack of in vitro effects of interferon on drug-metabolizing activity in the human liver

The in vitro effects of interferon (IFN) on drug—metabolizing activity in the human liver were investigated. The activities of 7-methoxycoumarin (7-MC) O-demethylase and 7-ethoxycoumarin (7-EC) Odeethylase in liver microsomes were measured in the absence and presence of IFN-a 2a. The peak blood concentration reached during clinical IFN-a 2a treatment has been reported to be 101 to 103 IU/ml. At a high concentration (106 IU/ml), IFN-a 2a inhibited the activities of both enzymes, to 75.6% and 72.4% of the control activity, respectively, but few effects were observed at concentrations of 101 to 105 IU/ml. These results indicate that the depression of drug metabolism during IFN treatment is not due to the direct inhibition of drug—metabolizing enzymes by IFN molecules, but that other factor(s) are needed for IFN to exhibit this action.