Levofloxacin pharmacokinetics and tissue residue concentrations after oral administration in Bilgorajska geese

ABSTRACT

1. The aim of this study was to assess the pharmacokinetics of levofloxacin, a third-generation fluoro-quinolone antimicrobial drug, in geese (n = 26) after either single intravenous or oral administration, and to evaluate the depletion profile in goose muscle, heart, liver, kidney and lung after a single oral dose.

2. The pharmacokinetic study involved 16 geese which were randomly divided into two groups (n = 8/group), the first received levofloxacin (2 mg/kg) intravenously while the second was treated with orally (5 mg/kg). The tissue depletion study involved 10 geese which were dosed orally (5 mg/kg) and two animals were killed at different time-points in order to collect the selected tissues. Levofloxacin was quantified in all the matrices tested by a validated high-performance liquid chromatography (HPLC) method, using a spectrofluorimetric detector. The pharmacokinetics were analysed using a non-compartmental model.

3. Plasma concentrations were quantified after up to 24 h in animals administered intravenously and up to 48 h after oral treatment. Levofloxacin was rapidly absorbed after oral administration (T_max = 0.38 h) showing high bioavailability (95.57 ± 20.61%). The drug showed a moderate volume of distribution (1.40 ± 0.28 ml/g) and rapid clearance (0.28 ± 0.06 ml/g/h). No statistical differences in estimates were found between the two different administration methods (P > 0.05). Drug residues were highest at 6 h and decreased constantly up to 48 h in all the selected tissues. Liver and kidney had the highest levofloxacin concentrations.

4. According to the pharmacokinetic/pharmacodynamic surrogate index (AUC/MIC) the levofloxacin dose regimen (after oral administration) used in the present study could be active against bacteria at a minimum inhibitory concentration (MIC) > 0.24  μg/ml in geese. In addition, drug accumulation in the liver might be controlled using an estimated preliminary withdrawal time of 90 h.

KEYWORDS:

• Pharmacokinetics
• levofloxacin
• goose
• organs
• HPLC

Acknowledgments

None of the authors has any financial or personal relationships that could inappropriately influence or bias the content of this paper. This work was supported by the University of Pisa (ex 60%). The authors are grateful to ThothPro for supplying the ThothPro software and Dr H. Owen (University of Queensland, Brisbane, Australia) for the scientific and English editing of the manuscript.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by the Università di Pisa [ex 60% 2017].