左氧氟沙星和莫西沙星对阿美替尼在大鼠体内的药代动力学影响

Effects of levofloxacin and moxifloxacin on the pharmacokinetic of almonertinib in rats

关键词:  左氧氟沙星  莫西沙星  阿美替尼  药代动力学  药物相互作用

Key words:  levofloxacin  moxifloxacin  almonertinib  pharmacokinetics  drug interactions

摘要:

目的 中考察左氧氟沙星和莫西沙星对阿美替尼在大鼠体内药代动力学的影响。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)，30min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(LC-MS/MS) 测定阿美替尼的血药浓度，比较各组间的药代动力学参数。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；Cmax分别为(29.2±6.93)、(51.12±15.93)和(81.97±31.96) μg·L-1；CLz/F分别为(82.28±23.14)、(25.50±9.53)和(17.21±4.05) L·h-1·kg-1；Vz/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2.2倍和1.7倍；联合莫西沙星后阿美替尼的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3.8倍和1.2倍，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代动力学特征。

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; Cmax was (29.2±6.93), (51.12±15.93) and (81.97±31.96) μg·L-1, respectively; CLz/F was (82.28±23.14), (25.50±9.53) and (17.21±4.05) L·h-1·kg-1, respectively; Vz/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 by 2.2 and 1.7-fold after administration of levofloxacin; the AUC, Cmax, Tmax and t1/2z increased by 3.7, 2.9, 2.4, 1.1-fold, respectively, while CLz/F and Vz/F decreased by 3.8 and 1.2-fold after administration of moxifloxacin, with statistically significant differences(P＜0.05). CONCLUSION The co-administration of levofloxacin and moxifloxacin significantly affected the pharmacokinetic profile of almonertinib in rats.