Drug–drug interactions between moxifloxacin and rifampicin based on pharmacokinetics in vivo in rats

Moxifloxacin and rifampicin are all the first‐line options for the treatment of active tuberculosis, which are often combined for the treatment of multidrug resistance pulmonary tuberculosis in clinic. However, the potential drug–drug interactions between moxifloxacin and rifampicin were unknown. The aim of this study was to investigate the drug–drug interactions between moxifloxacin and rifampicin based on their pharmacokinetics in vivo after oral administration of the single drug and both drugs, and reveal their mutual effects on their pharmacokinetics. Eighteen male Sprague–Dawley rats were randomly assigned to three groups: moxifloxacin group, rifampicin group and moxifloxacin + rifampicin group. Plasma concentrations of moxifloxacin and rifampicin were determined using LC‐MS at the designated time points after drug administration, and the main pharmacokinetic parameters were calculated. In addition, effects of moxifloxacin and rifampicin on their metabolic rate and absorption were investigated using rat liver microsome incubation systems and Caco‐2 cell transwell model. The main pharmacokinetic parameters of moxifloxacin including T_max, C_max, t_1/2 and AUC_(0–t) increased more in the moxifloxacin + rifampicin group than in the moxifloxacin group, but the difference was not significant (p > 0.05). However, the pharmacokinetic parameters of rifampicin, including peak concentration, area under the concentration–time curve, half‐life and the area under the first moment plasma concentration–time curve, increased significantly (p < 0.05) compared with the rifampicin group, and the time to peak concentration decreased significantly (p < 0.05). The mean residence time of rifampicin also increased in moxifloxacin + rifampicin group compared with the rifampicin group, but the difference was not significant (p > 0.05). The rat liver microsome incubation experiment indicated that moxifloxacin could increase the metabolic rate of rifampicin from 23.7 to 38.7 min. However, the Caco‐2 cell transwell experiment showed that moxifloxacin could not affect the absorption rate of rifampicin. These changes could enhance the drug efficacy, but they could also cause drug accumulation, which might induce adverse effect, so it was suggested that the drug dosage should be adjusted and the drug concentration in plasma should be monitored if moxifloxacin and rifampicin are co‐administered. Copyright © 2016 John Wiley & Sons, Ltd.