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

Abstract

The in vitro effects of interferon (IFN) on drugmetabolizing 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-α2a.
The peak blood concentration reached during clinical IFN-α2a treatment has been reported to be 10¹to 10³ IU/ml. At a high concentration (10⁶ IU/ml), IFN-α2a 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 res ults indicate that the depression of drug metabolism during IFN treatment is not due to the direct inhibition of drugmetabolizing enzymes by IFN molecules, but that other factor(s) are needed for IFN to exhibit this action.