Effect of Dexketoprofen on the Disposition Kinetics of Moxifloxacin in Plasma and Lung in Male and Female Rats

Background: The simultaneous use of NSAIDs and antibiotics is recommended for bacterial diseases in human and veterinary medicine. Moxifloxacin (MFX) and dexketoprofen (DEX) can be used simul-taneously in bacterial infections. However, there are no studies on how the simultaneous use of DEX affects the pharmacokinetics of MFX in rats. Objectives: The aim of this study was to determine the effect of DEX on plasma and lung pharmacokinetics of MFX in male and female rats. Methods: A total of 132 rats were randomly divided into 2 groups: MFX (n=66, 33 males/33 females) and MFX+DEX (n=66, 33 females/33 males). MFX at a dose of 20 mg/kg and DEX at a dose of 25 mg/kg were administered intraperitoneally. Plasma and lung concentrations of MFX were determined using the high-performance liquid chromatography-UV and pharmacokinetic parameters were evaluated by non-compartmental analysis. Results: Simultaneous administration of DEX increased the plasma and lung area under the curve from 0 to 8 h (AUC0-8) and peak concentration (Cmax) of MFX in rats, while it significantly decreased the total body clearance (CL/F). When female and male rats were compared, significant differences were detected in AUC0-8, Cmax, CL/F and volume of distribution. The AUC0-8lung/AUC0-8plasma ratios of MFX were calculated as 1.68 and 1.65 in female rats and 5.15 and 4.90 in male rats after single and combined use, respectively. Conclusion: MFX was highly transferred to the lung tissue and this passage was remarkably higher in male rats. However, DEX administration increased the plasma concentration of MFX in both male and female rats but did not change its passage to the lung. However, there is a need for a more detailed investigation of the difference in the pharmacokinetics of MFX in male and female rats.