Effects of interferon on drug metabolism.

Abstract

The induction and passive transfer of interferons have been shown to depress the level of cytochrome P-450 drug metabolism system of liver microsomes. Inducers of alpha or beta (Type I) interferons, such as Tilorone-HCl, statalon, mengovirus and others, suppressed the cytochrome P-450 system of rats or mice after administration. Induction of gamma (Type II) interferon also resulted in depression of the cytochrome P-450 system of mice. The gamma interferon was induced by sensitization of mice with Mycobacterium bovis strain BCG followed by challenge with tuberculin. The degree of depression of the cytochrome P-450 system correlated with the levels of interferon induced. In addition, passive transfer of exogenous gamma interferon also resulted in depression of the murine cytochrome-450 system. The metabolism of diphenylhydantoin, a drug metabolized by cytochrome-450, was examined in mice in which gamma interferon was induced. The metabolism of diphenylhydanoin was severely inhibited in mice which interferon was induced, and the level of inhibition correlated with the titer of gamma interferon induced. Passive transfer of gamma interferon also depressed the metabolism of diphenylhydantoin by murine cytochrome P-450.