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

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, T_max and t_1/2z 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.