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

作　　者：王智 付裕豪[1,2] 何雪茹 周鑫 李颖 董占军[2] WANG Zhi;FU Yuhao;HE Xueru;ZHOU Xin;LI Ying;DONG Zhanjun(Graduate School of Hebei Medical University,Shijiazhuang 050017,China;Department of Pharmacy,Hebei General Hospital,Shijiazhuang 050051,China)

机构地区：[1]河北医科大学研究生学院,石家庄050017 [2]河北省人民医院药学部,石家庄050051

出　　处：《中国现代应用药学》2025年第3期385-390,共6页Chinese Journal of Modern Applied Pharmacy

基　　金：河北省医学科学研究课题计划项目(20210037);河北省自然科学基金联合基金项目(H2022307063)。

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AUC_(0-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(C_(max))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,C_(max)增加了75%,而CL_(z/F)和V_(z/F)分别降低了69%和62%;联合莫西沙星给药后阿美替尼的AUC、C_(max)、Tmax、t1/2z分别增加了3.7、2.9、2.4、1.1倍,而CL_(z/F)和V_(z/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。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:AUC_(0-t) was(194.47±53.42),(659.06±237.85)and(903.42±209.47)μg·L^(-1)·h,respectively;peak concentration(C_(max))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 C_(max) increased by 75%,while CL_(z/F) and V_(z/F) decreased 69%and 62%after combined administration of levofloxacin;the AUC,C_(max),Tmax and t1/2z of almonertinib increased by 3.7,2.9,2.4,1.1-fold,respectively,while CL_(z/F) and V_(z/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.

关 键 词：左氧氟沙星 莫西沙星 阿美替尼 药动学 药物相互作用 

分 类 号：R969.1[医药卫生—药理学]