Comparisons of plasma and fecal pharmacokinetics of danofloxacin and enrofloxacin in healthy and Mannheimia haemolytica infected calves

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Feyisa Beyi, Ashenafi
Magnin, Géraldine
Hawbecker, Tyler
Slagel, Clare
Dewell, Renee
Sahin, Orhan
Coetzee, Johann F.
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Veterinary Microbiology and Preventive MedicineVeterinary Diagnostic and Production Animal MedicineBiomedical SciencesCenter for Food Security and Public Health
Danofloxacin and enrofloxacin are fluoroquinolones (FQs) used to treat and control bovine respiratory disease (BRD) complex. While low toxicity, high bactericidal activity, and availability in single and multiple dosing regimens make them preferable, the increasing incidence of FQ-resistance in foodborne pathogens and effects on gut microbiota necessitate evaluating their pharmacokinetics (PKs). The objective of this study was to determine the exposure level of gut microbiota to subcutaneously administered FQs and compare their PKs between plasma and feces in healthy and Mannheimia haemolytica infected calves. A single dose of danofloxacin (8 mg/kg), low dose (7.5 mg/kg), or high dose (12.5 mg/kg) of enrofloxacin was administered to calves. Blood and feces were collected from calves under experimental conditions over 48 h, and FQ concentrations were measured using Ultra High-Pressure Liquid Chromatography. While moderate BRD signs were exhibited in most calves in the infected cohorts, the plasma PKs were similar between healthy and sick calves. However, the fecal danofloxacin concentration was lower in the BRD group (area under concentration–time curve [AUCinf], BRD median = 2627, healthy median = 2941 h*μg/mL, adj.P = 0.005). The dose normalized plasma and fecal danofloxacin concentrations were higher than those of enrofloxacin and its metabolite ciprofloxacin. Further, FQs had several fold higher overall concentrations in feces than in plasma in both groups. In conclusion, parenterally administered FQs expose gut microbiota to high concentrations of the antibiotics.
This article is published as Beyi, Ashenafi Feyisa, Jonathan P. Mochel, Géraldine Magnin, Tyler Hawbecker, Clare Slagel, Grant Dewell, Renee Dewell et al. "Comparisons of plasma and fecal pharmacokinetics of danofloxacin and enrofloxacin in healthy and Mannheimia haemolytica infected calves." Scientific Reports 12, no. 1 (2022): 1-13. DOI: 10.1038/s41598-022-08945-z. Copyright 2022 The Author(s). Attribution 4.0 International (CC BY 4.0). Posted with permission.