Influence of N-Acetyl-L-Cysteine on the Pharmacokinetics and Antibacterial Activity of Marbofloxacin in Chickens

Background/Objectives: Marbofloxacin, a second-generation fluoroquinolone, is used to control economically significant poultry diseases caused by pathogenic bacteria such as Staphylococcus aureus and Escherichia coli. Although synergistic antimicrobial activity between fluoroquinolones and N-acetyl-L-cysteine (NAC) has been observed in vitro, data on their pharmacokinetic interactions in vivo remain limited. This study aimed to evaluate the effect of NAC on the oral pharmacokinetics of marbofloxacin in broiler chickens and its antibacterial activity against E. coli ATCC 25922 and S. aureus ATCC 25923, assessing the potential benefits of their combined administration. Methods: Marbofloxacin pharmacokinetics was evaluated in broilers (5 mg/kg dose) after single intravenous (n=12) or single oral (n=12) administration into the crop; co-administration with NAC (400 mg/kg via feed): first day poultry (n=12) received single oral dose of marbofloxacin via the crop and next days the fluoroquinoilone drug was administered via drinking water. Plasma levels were determined by LC-MS/MS analysis and minimum inhibitory concentrations were assessed using the microbroth dilution method. Results: NAC significantly reduced bioavailability of marbofloxacin after a single oral administration into the crop and decreased the elimination rate constant following multiple administration of both drugs. At a concentration of 20 μg/mL, NAC led to a 3.8-fold reduction in the MIC of marbofloxacin against E. coli ATCC 25922 and a two-fold decrease at concentrations between 1 μg/mL and 6 μg/mL, while no change was observed for S. aureus ATCC 25923. Conclusions: Oral co-administration of NAC and marbofloxacin reduced fluoroquinolone bioavailability by two-fold while enhancing antibacterial activity against E. coli ATCC 25922.