Monostory K, Vereczkey L
Central Research Institute for Chemistry, Hungarian Academy of Sciences, Budapest.
Eur J Drug Metab Pharmacokinet. 1995 Jan-Mar;20(1):43-7. doi: 10.1007/BF03192287.
The effect of ipriflavone administered at a dose of 25 mg/kg and 100 mg/kg and coadministered with theophylline was investigated in selective assays of particular P450 isoenzyme activities. Significant changes could be detected in the activities of CYP2E1 and CYP3A in liver microsomes from male Wistar rats treated with ipriflavone. Induction of CYP2E1 was shown by aniline or p-nitro-phenol hydroxylation as a result of ipriflavone treatment. Aniline hydroxylation activity of CYP2E1 was induced by theophylline + ipriflavone (100 mg/kg) coadministration as well. It should be noted that theophylline does not cause alteration in CYP2E1 activity. On the other hand, ipriflavone inhibited ethylmorphine and aminopyrine N-demethylation activities catalysed by CYP3A. An additional effect in the inhibition of aminopyrine N-demethylation could be observed in microsomes from theophylline + ipriflavone treated groups. Our results suggest that the decrease in theophylline metabolism increasing level of serum theophylline of theophylline-treated patient during ipriflavone administration [Takahashi J. et al. (1992): Eur. J. Clin. Pharmacol., 43, 207-208] may be related to CYP3A inhibition by ipriflavone.
在特定P450同工酶活性的选择性测定中，研究了以25毫克/千克和100毫克/千克剂量给药的异黄酮以及与茶碱共同给药的效果。在用异黄酮处理的雄性Wistar大鼠肝脏微粒体中，可检测到CYP2E1和CYP3A活性的显著变化。异黄酮处理导致苯胺或对硝基苯酚羟基化，表明其对CYP2E1有诱导作用。茶碱 + 异黄酮（100毫克/千克）共同给药也诱导了CYP2E1的苯胺羟基化活性。应当指出，茶碱不会引起CYP2E1活性的改变。另一方面，异黄酮抑制了CYP3A催化的乙基吗啡和氨基比林N-去甲基化活性。在茶碱 + 异黄酮处理组的微粒体中，可观察到对氨基比林N-去甲基化抑制的额外作用。我们的结果表明，在异黄酮给药期间，茶碱治疗患者的茶碱代谢降低、血清茶碱水平升高[高桥J.等人（1992年）：《欧洲临床药理学杂志》，43，207 - 208]可能与异黄酮对CYP3A的抑制有关。
