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    左氧氟沙星和莫西沙星对阿美替尼在大鼠体内的药动学影响

    Effects of Levofloxacin and Moxifloxacin on the Pharmacokinetic of Almonertinib in Rats

      摘要
    • 摘要:
      目的  考察左氧氟沙星和莫西沙星对阿美替尼在大鼠体内药动学的影响。
      方法 将18只大鼠随机分为3组，组1先灌胃0.5%羧甲基纤维素钠，组2先灌胃左氧氟沙星(70 mg·kg−1)，组3先灌胃莫西沙星(40 mg·kg−1)，30 min后各组分别再灌胃阿美替尼(15 mg·kg−1)，采用液相色谱-串联质谱法测定阿美替尼的血药浓度，比较各组间的药动学参数。
      结果 组1、组2和组3中阿美替尼的AUC0-t分别为(194.47±53.42)、(659.06±237.85)和(903.42±209.47) μg·L−1·h；最大血药浓度(Cmax)分别为(29.22±6.93)、(51.12±15.93)和(81.97±31.96) μg·L−1；清除率(clearance，CL)z/F分别为(82.28±23.14)、(25.50±9.53)和(17.21±4.05) L·h−1·kg−1；表观分布容积(apparent volume of distribution，V)z/F分别为(358.37±141.80)、(134.53±63.74)和(160.01±87.25) L·kg−1。与对照组相比，联合左氧氟沙星给药后阿美替尼的AUC增加了2.4倍，Cmax增加了75%，而CLz/F和Vz/F 分别降低了69%和62%；联合莫西沙星给药后阿美替尼的AUC、Cmax、Tmax、t1/2z分别增加了3.7、2.9、2.4、1.1倍，而CLz/F和Vz/F 分别降低了79%和55%，差异均有统计学意义(均P<0.05)。
      结论 联合应用左氧氟沙星或莫西沙星可显著影响大鼠体内阿美替尼药动学特征。

       

      Abstract:
      OBJECTIVE To investigate the effects of administration of levofloxacin and moxifloxacin on the pharmacokinetics of almonertinib in rats.
      METHODS Eighteen rats were randomly divided into three groups, rats in group 1 were gavaged with 0.5% sodium carboxymethylcellulose, rats in group 2 were gavaged with levofloxacin(70 mg·kg−1), rats in group 3 were gavaged with moxifloxacin(40 mg·kg−1), and after 30 min each group were then gavaged with almonertinib(15 mg·kg−1), respectively. Plasma concentrations of almonertinib were determined by LC-MS/MS and pharmacokinetic parameters were compared between the groups.
      RESULTS The main pharmacokinetic parameters of almonertinib in group 1, 2, and 3 were obtained as follows: AUC0-t was (194.47±53.42), (659.06±237.85) and (903.42±209.47) μg·L−1·h, respectively; peak concentration(Cmax) was (29.22±6.93), (51.12±15.93) and (81.97±31.96) μg·L−1, respectively; clearance(CL)z/F was (82.28±23.14), (25.50±9.53) and (17.21±4.05) L·h−1·kg−1, respectively; apparent volume of distribution(V)z/F was (358.37±141.80), (134.53±63.74) and (160.01±87.25) L·kg−1, respectively. Compared with the control group, the AUC of almonertinib increased by 2.4 fold, and Cmax increased by 75%, while CLz/F and Vz/F decreased 69% and 62% after combined administration of levofloxacin; the AUC, Cmax, Tmax and t1/2z of almonertinib increased by 3.7, 2.9, 2.4, 1.1-fold, respectively, while CLz/F and Vz/F decreased 79% and 55% after combined administration of moxifloxacin with statistically significant differences(all P<0.05).
      CONCLUSION The combined administration of levofloxacin and moxifloxacin significantly affectes the pharmacokinetic profile of almonertinib in rats.

       

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