Monostory K, Vereczkey L
Central Research Institute for Chemistry, Hungarian Academy of Sciences, Budapest, Hungary.
Eur J Drug Metab Pharmacokinet. 1996 Jan-Mar;21(1):61-6. doi: 10.1007/BF03190279.
The effect of ipriflavone and its major metabolites, 7-hydroxy-isoflavone and 7-(1-carboxy-ethoxy)-isoflavone on theophylline metabolism was examined in vitro in human liver microsomes. The compounds inhibited the N-demethylation to 1- or 3-methylxanthine, the major pathway of theophylline metabolism. The effect showed concentration dependence. The oxidation of theophylline to 1,3-dimethyluric acid was slightly affected by ipriflavone and its metabolites and the effect was non-specific. Results indicate that the reduction of theophylline clearance by concomitant ipriflavone administration observed by Takahashi et al. [Takahashi J., Kawakatsu K., Wakayama T., Sawaoka H. (1992): Elevation of serum theophylline levels by ipriflavone in a patient with chronic obstructive pulmonary disease. Eur. J. Clin. Pharmacol., 43, 207-208] is primarily due to an interaction of the inhibitory ipriflavone and/or its metabolites with cytochrome P450 enzyme(s) that mediate N-demethylation of theophylline.
在人肝微粒体中对依普黄酮及其主要代谢产物7-羟基异黄酮和7-(1-羧基乙氧基)异黄酮对茶碱代谢的影响进行了体外研究。这些化合物抑制了茶碱代谢的主要途径——N-去甲基化生成1-或3-甲基黄嘌呤。该作用呈浓度依赖性。依普黄酮及其代谢产物对茶碱氧化生成1,3-二甲基尿酸的影响较小，且该作用是非特异性的。结果表明，高桥等人[高桥J.、川胜K.、若山T.、泽冈H.（1992年）：依普黄酮使慢性阻塞性肺疾病患者血清茶碱水平升高。欧洲临床药理学杂志，43，207 - 208]观察到的同时给予依普黄酮导致茶碱清除率降低，主要是由于具有抑制作用的依普黄酮和/或其代谢产物与介导茶碱N-去甲基化的细胞色素P450酶相互作用所致。
