Effects of Human Recombinant Interferon-α2b on P450-Dependent Isozymes in Rat Liver and Skin

Abstract

Adult female Wistar rats divided into two groups (6 animals each) were subcutaneously treated with 10(5) units/day recombinant human interferon-alpha 2b (hrIFN-alpha 2b) and corresponding quantities of the vehicle, respectively, over a period of 7 days. Microsomal protein, P450 content, and the activities of aminopyrine-N-demethylase (ADM), 7-ethoxyresofurin-O-deethylase (7-ERO-D) and of erythromycin-N-demethylase (EMDM) were determined in the liver microsomes. Moreover, 7-ERO-D and EMDM activities were determined in the skin microsomes of the treated animals. In the liver microsomes hrIFN-alpha 2b caused a statistically significant increase in ADM activity and a statistically significant decrease in 7-ERO-D and EMDM activities, as compared to the controls. However, in the pooled skin microsomes 7-ERO-D activity showed a trend to increase under the administration of hrIFN-alpha 2b, whereas EMDM activity could not be detected in the treated or the control animals. The results of the present study indicate that hrIFN-alpha 2b is capable of affecting the activities of P450-dependent isozymes in the rat liver and skin in a different manner. Our findings support the hypothesis that clinically relevant interactions may occur during the concomitant administration of hrIFN-alpha 2b and other compounds that are metabolized by hepatic and cutaneous P450 monooxygenases.