Goerz G, Tsambaos D, Schuppe H C, Bolsen K, Georgiou S, Reinauer S, Zografakis C
Department of Dermatology, Heinrich Heine University of Düsseldorf, Germany.
Skin Pharmacol. 1995;8(3):162-6. doi: 10.1159/000211341.
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.
将成年雌性Wistar大鼠分为两组（每组6只），分别皮下注射10(5)单位/天的重组人干扰素α-2b（hrIFN-α2b）和相应剂量的赋形剂，持续7天。测定肝微粒体中的微粒体蛋白、P450含量以及氨基比林-N-脱甲基酶（ADM）、7-乙氧基异吩恶唑酮-O-脱乙基酶（7-ERO-D）和红霉素-N-脱甲基酶（EMDM）的活性。此外，还测定了受试动物皮肤微粒体中的7-ERO-D和EMDM活性。与对照组相比，在肝微粒体中，hrIFN-α2b使ADM活性有统计学意义的增加，使7-ERO-D和EMDM活性有统计学意义的降低。然而，在合并的皮肤微粒体中，hrIFN-α2b给药后7-ERO-D活性有增加的趋势，而在受试动物或对照动物的皮肤微粒体中均未检测到EMDM活性。本研究结果表明，hrIFN-α2b能够以不同方式影响大鼠肝脏和皮肤中P450依赖性同工酶的活性。我们的研究结果支持这样一种假设，即在同时给予hrIFN-α2b和其他由肝脏和皮肤P450单加氧酶代谢的化合物时，可能会发生临床相关的相互作用。
