Valero F, de la Torre R, Segura J
Department of Pharmacology and Toxicology, Institut Municipal d'Investigació Mèdica, Barcelona, Spain.
J Pharm Pharmacol. 1991 Jan;43(1):17-21. doi: 10.1111/j.2042-7158.1991.tb05440.x.
The in-vitro inhibition of several metabolic pathways has been studied in 3-methylcholanthrene-treated rats. The specificity of the 7-ethoxyresorufin O-de-ethylase reaction has been determined in the presence and absence of ciprofloxacin, enoxacin, norfloxacin, ofloxacin, nalidixic acid, oxolinic acid and pipemidic acid. For the caffeine N3-demethylation reaction, enoxacin and pipemidic acid were used. Enoxacin (IC50 = 105 microM, Ki = 65 microM) and pipemidic acid (IC50 = 115 microM, Ki = 160 microM) significantly inhibited 7-ethoxyresorufin O-de-ethylase reaction and caffeine N3-demethylation (IC50 = 60 microM for enoxacin and IC50 = 185 microM for pipemidic acid) by a competitive mechanism. Other quinolones had lower or no (ofloxacin) inhibitory capacity. The order of inhibitory activity observed is in agreement with results obtained previously from in-vivo studies in man. No activity was detected towards ethylmorphine N-demethylation.
已对3-甲基胆蒽处理的大鼠体内几种代谢途径的体外抑制作用进行了研究。在有和没有环丙沙星、依诺沙星、诺氟沙星、氧氟沙星、萘啶酸、恶喹酸和吡哌酸存在的情况下，测定了7-乙氧基试卤灵O-脱乙基酶反应的特异性。对于咖啡因N3-去甲基化反应，使用了依诺沙星和吡哌酸。依诺沙星（IC50 = 105微摩尔，Ki = 65微摩尔）和吡哌酸（IC50 = 115微摩尔，Ki = 160微摩尔）通过竞争机制显著抑制7-乙氧基试卤灵O-脱乙基酶反应和咖啡因N3-去甲基化（依诺沙星的IC50 = 60微摩尔，吡哌酸的IC50 = 185微摩尔）。其他喹诺酮类药物的抑制能力较低或无抑制能力（氧氟沙星）。观察到的抑制活性顺序与先前在人体进行的体内研究结果一致。未检测到对N-乙基吗啡去甲基化的活性。
