WCK 771 (INN: levonadifloxacin) is a novel antibacterial agent belonging to benzoquinolizine subclass of fluoroquinolones which is under clinical development as a parenteral formulation and its prodrug WCK 2349 (INN: alalevonadifloxacin) as an oral option. Both the drugs have been approved recently in India based on phase III trial completed for ABSSSI.

In vitro CYP inhibition potential of levonadifloxacin and its sulfate metabolite (WCK 2146) were assessed in this study. The inhibitory effects of levonadifloxacin and its sulfate metabolite were assessed for seven key human liver CYP isoforms 1A2, 2B6, 2C8, 2C9, 2C19, 2D6 and 3A4 using human liver microsome (HLM) employing validated LC-MS/MS method.

The results showed that levonadifloxacin and its metabolite did not inhibit enzyme activity of any of the key CYP isoforms (1A2, 2B6, 2C8, 2C9, 2C19, 2D6 and 3A4) even at supra therapeutic concentrations (12–24X, Clinical Cmax: 25–35µg/mL).

These in vitro CYP inhibition studies of levonadifloxacin and its sulfate metabolite indicate lack of potential for pharmacokinetic drug interactions of levonadifloxacin when co-administered with drugs which are substrate of these isoforms. Therefore, further clinical studies evaluating CYP mediated drug–drug interactions are not warranted for levonadifloxacin and alalevonadifloxacin.

WCK 771（INN：levonadifloxacin）是属于氟喹诺酮类的苯醌喹嗪亚类的新型抗菌剂，目前正在作为胃肠外制剂进行临床开发，其前药WCK 2349（INN：alalevonadifloxacin）也可以口服。根据ABSSSI已完成的III期临床试验，这两种药物最近已在印度获得批准。

这项研究评估了levonadifloxacin及其硫酸盐代谢产物（WCK 2146）的体外CYP抑制潜能。使用已验证的LC-MS / MS方法，使用人肝微粒体（HLM）评估了levonadifloxacin及其硫酸盐代谢产物对7种关键的人肝CYP亚型1A2、2B6、2C8、2C9、2C19、2D6和3A4的抑制作用。

结果表明，即使在超治疗浓度（12–24X，临床Cmax：25–25）时，levonadifloxacin及其代谢物也不会抑制任何关键CYP亚型（1A2、2B6、2C8、2C9、2C19、2D6和3A4）的酶活性。 35µg / mL）。

这些对levonadifloxacin及其硫酸盐代谢物的体外CYP抑制研究表明，当与这些亚型的底物药物共同给药时，levonadifloxacin的药代动力学药物相互作用缺乏潜力。因此，尚无必要进一步评估CYP介导的药物-药物相互作用的临床研究用于levonadifloxacin和alalevonadifloxacin。