Effects of human recombinant interferon-alpha 2b 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 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.
Goerz
G
G
Department of Dermatology, Heinrich Heine University of Düsseldorf, Germany.
Tsambaos
D
D
Schuppe
H C
HC
Bolsen
K
K
Georgiou
S
S
Reinauer
S
S
Zografakis
C
C
D000633:Aminopyrine N-Demethylase / Q000378:metabolism; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D019363:Cytochrome P-450 CYP1A1; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D005260:Female; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology*; D007527:Isoenzymes / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D010088:Oxidoreductases / Q000378:metabolism; D010089:Oxidoreductases, N-Demethylating / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins; D012867:Skin / Q000187:drug effects / Q000201:enzymology*
D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007527:Isoenzymes; D011994:Recombinant Proteins; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D001189:Aryl Hydrocarbon Hydroxylases; D019363:Cytochrome P-450 CYP1A1; D051544:Cytochrome P-450 CYP3A; D010089:Oxidoreductases, N-Demethylating; D000633:Aminopyrine N-Demethylase