Journal List > J Vet Sci > v.21(2) > 1148354

Sitovs, Voiko, Kustovs, Kovalcuka, Bandere, Purvina, and Giorgi: Pharmacokinetic profiles of levofloxacin after intravenous, intramuscular and subcutaneous administration to rabbits (Oryctolagus cuniculus)

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 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.

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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.
jvs-21-e32f1.tif
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.
jvs-21-e32f2.tif
Table 1.
Mean (± SD) pharmacokinetic parameters of levofloxacin in plasma following I/V, I/M or S/C administration to rabbits at a dose of 5 mg/kg bodyweight
PK parameters Units I/V (n = 6) I/M (n = 6) S/C (n = 4)
AUC0−last mg* h/L 9.03 ± 2.66 9.07 ± 1.80 9.28 ± 1.56
AUC0−inf * mg* h/L 9.08 ± 2.64 9.07 ± 1.80 9.31 ± 1.50
AUMC0−last * mg* h* h/L 22.93 ± 12.46 37.87 ± 18.35* 36.62 ± 17.35
AUMC0−inf mg* h* h/L 23.64 ± 12.17 37.89 ± 18.34* 36.98 ± 16.82
C max μ g/mL N/A 3.33 ± 0.39 2.91 ± 0.56
C first μ g/mL 7.13 ± 1.47 N/A N/A
t max MEDIAN h N/A 0.50 (0.08–0.75) 0.75
t1/2λ z HM h 2.06 ± 0.18 2.01 ± 0.24 1.80 ± 0.14
λ z 1/h 0.34 ± 0.03 0.34 ± 0.04 0.39 ± 0.03
MRT0−last HM h 2.19 ± 0.83 3.75 ± 1.16* 3.44 ± 1.31
MRT0−inf HM h 2.27 ± 0.80 3.75 ± 1.16* 3.52 ± 1.25
MAT HM h N/A 1.29 ± 0.61 0.45 ± 1.47
Cl mL/g* h 0.60 ± 0.18 N/A N/A
Cl/F mL/g* h N/A 0.57 ± 0.11 0.55 ± 0.10
V ss mL/g 1.37 ± 0.39 N/A N/A
V area/F mL/g N/A 1.66 ± 0.34 1.42 ± 0.18
F % N/A 105.69 ± 27.50 118.93 ± 40.51

PK, pharmacokinetic; AUC0−last, area under the plasma-concentration time curve from zero to the last quantified sampling point time; AUC0-inf, area under the plasma-concentration time curve from zero extrapolated to infinity; AUMC0−last, area under the first moment curve from zero to the last quantified sampling point time; AUMC0−inf, area under the first moment curve from zero extrapolated to infinity; C max, maximum plasma drug concentration; C first, concentration at first sample collection point; t max, time of the maximum plasma concentration; t1/2λ z, half-life of the elimination part of the curve; λ z, slope of the elimination part of the curve; MRT0−last, mean residence time from zero to the last quantified sampling point time; MRT0−inf, mean residence time from zero extrapolated to infinity; MAT, mean absorption time; Cl, total plasma clearance; Cl/F, plasma clearance corrected to the bioavailability; V ss, volume of distribution at steady-state; V area/F, volume of distribution corrected to the bioavailability; n, number of experimental animals receiving levofloxacin via the corresponding route of administration; I/V, intravenous; I/M, intramuscular; S/C, subcutaneous; N/A, not applicable; HM, harmonic mean.* Significantly different from I/V administration (p < 0.05);

Range reported.

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