J Vet Sci.  2020 Mar;21(2):e32. 10.4142/jvs.2020.21.e32.

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

Affiliations
  • 1Department of Pharmacology, Riga Stradins University, Riga, LV-1007, Latvia
  • 2Clinical Institute, Faculty of Veterinary Medicine, University of Life Sciences and Technologies, Jelgava, LV-3001, Latvia
  • 3Department of Pharmaceutical Chemistry, Riga Stradins University, Riga, LV-1007, Latvia
  • 4Department of Veterinary Sciences, University of Pisa, Pisa 56126, Italy

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 AUC 0-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 µg/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 µg/mL.

Keyword

Levofloxacin; rabbits; pharmacokinetics; tears; osmolar concentration

Figure

  • Fig. 1. Semilogarithmic plots of average levofloxacin plasma concentrations in rabbits (error bars represent standard deviations) after I/V (n = 6), I/M (n = 6), and S/C (n = 4) levofloxacin administration of 5 mg/kg bodyweight. I/V, intravenous; I/M, intramuscular; S/C, subcutaneous.

  • Fig. 2. Changes in tear osmolarity in rabbits after a single 5 mg/kg levofloxacin dose administered via I/V (n = 6), I/M (n = 6), or S/C (n = 4) routes (mean values indicated; error bars represent standard deviation). I/V, intravenous; I/M, intramuscular; S/C, subcutaneous.


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