EFFECTS OF HUMAN RECOMBINANT INTERFERON-A2B ON P450-DEPENDENT ISOZYMES IN RAT-LIVER AND SKIN

Adult female Wistar rats divided into two groups (6 animals each) were subcutaneously treated with 10(5) units/day recombinant human interfe ron-alpha 2b (hrIFN-alpha 2b) and corresponding quantities of the vehi cle, respectively, over a period of 7 days. Microsomal protein, P450 c ontent, and the activities of aminopyrine-N-demethylase (ADM), 7-ethox yresorufin-O-deethylase (7-ERO-D) and of erythromycin-N-demethylase (E MDM) were determined in the liver microsomes. Moreover, 7-ERO-D and EM DM activities were determined in the skin microsomes of the treated an imals. In the liver microsomes hrIFN-alpha 2b caused a statistically s ignificant increase in ADM activity and a statistically significant de crease in 7-ERO-D and EMDM activities, as compared to the controls. Ho wever, in the pooled skin microsomes 7-ERO-D activity showed a trend t o increase under the administration of hrIFN-alpha 2b, whereas EMDM ac tivity could not be detected in the treated or the control animals. Th e results of the present study indicate that hrIFN-alpha 2b is capable of affecting the activities of P450-dependent isozymes in the rat liv er and skin in a different manner. Our findings support the hypothesis that clinically relevant interactions may occur during the concomitan t administration of hrIFN-alpha 2b and other compounds that are metabo lized by hepatic and cutaneous P450 monooxygenases.