Pharmacokinetics and residue depletion of enrofloxacinand its metabolite ciprofloxacin in land snails(Cornu aspersum maxima)

Abstract

Introduction: The pharmacokinetics (PK) and tissue distribution of enrofloxacin (EF) and its main metabolite, ciprofloxacin (CP), were determined in land snails (Cornu aspersum maxima) dosed singly and multiply orally or intrahaemolymphatically (IHL). Material and Methods: In the single-dose regimen, snails received EF via IHL injection (1 mg/kg), gavage (30 mg/kg) or medicated wafer (30 mg/kg). Haemolymph was sampled up to 72 h post administration. In the multiple-dose regimen, snails were treated with 10 mg/kg EF via gavage for five days. Tissues and body fluids were sampled up to 240 h. Ultra-high-performance liquid chromatography–tandem mass spectrometry simultaneously determined the concentrations of EF and CP. Results: Concentrations of EF in haemolymph after IHL administration remained above the limit of quantification up to 72 h post dose. Enrofloxacin had a 15–19 h elimination half-life. It was more bioavailable from medicated wafers (74.6%) than from gavage (27.7%); however, variability and small sample sizes prevented statistical analysis. Concentrations of CP were inconsistently detectable and often below quantification limits, suggesting limited EF biotransformation. After multiple dosing, EF accumulated predominantly in the hepatopancreas, and less in muscle, the albumen gland and mucus. Tissue contained detectable CP but haemolymph did not. Persistence of EF was noted in tissues beyond 240 h at concentrations often exceeding the 100–300 μg/kg maximum residue limits for other food-producing species. Conclusion: This preliminary study indicates that EF clears slowly and metabolises incompletely to CP in snails, resembling its PK patterns in aquatic and reptilian species. The persistence of EF in edible tissues suggests that withdrawal periods may need to be considerably longer than those for other terrestrial animals. Further depletion studies with extended sampling times, assessment of minimum inhibitory concentration values for snail pathogens and protein binding data are warranted to support safe and rational EF use in heliciculture.