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Pharmacokinetic profiles of levofloxacin after intravenous, intramuscular and subcutaneous administration to rabbits (Oryctolagus cuniculus)

  • Sitovs, Andrejs (Department of Pharmacology, Riga Stradins University) ;
  • Voiko, Laura (Clinical Institute, Faculty of Veterinary Medicine, University of Life Sciences and Technologies) ;
  • Kustovs, Dmitrijs (Department of Pharmacology, Riga Stradins University) ;
  • Kovalcuka, Liga (Clinical Institute, Faculty of Veterinary Medicine, University of Life Sciences and Technologies) ;
  • Bandere, Dace (Department of Pharmaceutical Chemistry, Riga Stradins University) ;
  • Purvina, Santa (Department of Pharmacology, Riga Stradins University) ;
  • Giorgi, Mario (Department of Veterinary Sciences, University of Pisa)
  • Received : 2019.12.20
  • Accepted : 2020.01.22
  • Published : 2020.03.31

Abstract

Levofloxacin pharmacokinetic profiles were evaluated in 6 healthy female rabbits after intravenous (I/V), intramuscular (I/M), or subcutaneous (S/C) administration routes at a single dose of 5 mg/kg in a 3 × 3 cross-over study. Plasma levofloxacin concentrations were detected using a validated Ultra Performance Liquid Chromatography method with a fluorescence detector. Levofloxacin was quantifiable up to 10 h post-drug administration. Mean AUC0-last values of 9.03 ± 2.66, 9.07 ± 1.80, and 9.28 ± 1.56 mg/h*L were obtained via I/V, I/M, and S/C, respectively. Plasma clearance was 0.6 mL/g*h after I/V administration. Peak plasma concentrations using the I/M and S/C routes were 3.33 ± 0.39 and 2.91 ± 0.56 ㎍/mL. Bioavailability values, after extravascular administration were complete, - 105% ± 27% (I/M) and 118% ± 40% (S/C). Average extraction ratio of levofloxacin after I/V administration was 7%. Additionally, levofloxacin administration effects on tear production and osmolarity were evaluated. Tear osmolarity decreased within 48 h post-drug administration. All 3 levofloxacin administration routes produced similar pharmacokinetic profiles. The studied dose is unlikely to be effective in rabbits; however, it was calculated that a daily dose of 29 mg/kg appears effective for I/V administration for pathogens with MIC < 0.5 ㎍/mL.

Keywords

Acknowledgement

The authors sincerely thank Dr. Victoria Llewellyn (James Cook University, Australia) for manuscript grammar correction and the ThothPro (Gdansk, Poland) team for software supply. This work was supported by Riga Stradins University doctorate grants.

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