Kim Kyoung-Ah, Park Ji-Young
East-West Medical Research Institute, Kyunghee University, Seoul, Korea.
Drug Metab Dispos. 2003 Sep;31(9):1090-2. doi: 10.1124/dmd.31.9.1090.
The inhibitory effect of glyburide [International Nonproprietary Name (INN), glibenclamide] on CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4 activities was evaluated using pooled human liver microsomes. Glyburide strongly inhibited CYP2C9-catalyzed S-warfarin and phenytoin metabolism in a competitive manner, with Ki (IC50) values of 2.4 (11.3) microM and 3.1 (9.4) microM, respectively. CYP3A4-catalyzed midazolam 1-hydroxylation was inhibited by glyburide with a Ki (IC50) value of 42.5 (90.0) microM. However, glyburide showed no appreciable inhibitory effect on CYP1A2, CYP2C8, CYP2C19, CYP2E1, or CYP2D6. In summary, glyburide showed potent inhibition on CYP2C9 and weak inhibition on CYP3A4, whereas it had minimal or no inhibitory effect on the other cytochromes p450 examined. It is anticipated that clinically significant drug-drug interactions will ensue when glyburide is coadministered with agents that are cleared primarily by the CYP2C9-mediated pathway and those with narrow therapeutic ranges.
使用人肝微粒体池评估了格列本脲[国际非专利药名（INN），优降糖]对CYP1A2、CYP2C8、CYP2C9、CYP2C19、CYP2D6、CYP2E1和CYP3A4活性的抑制作用。格列本脲以竞争性方式强烈抑制CYP2C9催化的S-华法林和苯妥英代谢，其Ki（IC50）值分别为2.4（11.3）微摩尔和3.1（9.4）微摩尔。格列本脲抑制CYP3A4催化的咪达唑仑1-羟化反应，Ki（IC50）值为42.5（90.0）微摩尔。然而，格列本脲对CYP1A2、CYP2C8、CYP2C19、CYP2E1或CYP2D6未显示出明显的抑制作用。总之，格列本脲对CYP2C9有强效抑制作用，对CYP3A4有弱抑制作用，而对其他检测的细胞色素P450的抑制作用极小或无抑制作用。预计当格列本脲与主要通过CYP2C9介导途径清除的药物以及治疗窗窄的药物合用时，会发生具有临床意义的药物相互作用。
