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Pharmacokinetics of levofloxacin after single intravenous, oral and subcutaneous administration to dogs
Author(s) -
Landoni Maria Fabiana,
Albarellos Gabriela Alejandra
Publication year - 2019
Publication title -
journal of veterinary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.527
H-Index - 60
eISSN - 1365-2885
pISSN - 0140-7783
DOI - 10.1111/jvp.12726
Subject(s) - pharmacokinetics , levofloxacin , bioavailability , oral administration , volume of distribution , pharmacology , medicine , distribution (mathematics) , absorption (acoustics) , antibiotics , chemistry , mathematical analysis , biochemistry , physics , mathematics , acoustics
The pharmacokinetic properties of the fluoroquinolone levofloxacin ( LFX ) were investigated in six dogs after single intravenous, oral and subcutaneous administration at a dose of 2.5, 5 and 5 mg/kg, respectively. After intravenous administration, distribution was rapid ( T ½dist 0.127 ± 0.055 hr) and wide as reflected by the volume of distribution of 1.20 ± 0.13 L/kg. Drug elimination was relatively slow with a total body clearance of 0.11 ± 0.03 L kg −1 hr −1 and a T ½ for this process of 7.85 ± 2.30 hr. After oral and subcutaneous administration, absorption half‐life and T max were 0.35 and 0.80 hr and 1.82 and 2.82 hr, respectively. The bioavailability was significantly higher ( p ˂ 0.05) after subcutaneous than oral administration (79.90 vs. 60.94%). No statistically significant differences were observed between other pharmacokinetic parameters. Considering the AUC 24 hr / MIC and C max / MIC ratios obtained, it can be concluded that LFX administered intravenously (2.5 mg/kg), subcutaneously (5 mg/kg) or orally (5 mg/kg) is efficacious against Gram‐negative bacteria with MIC values of 0.1 μg/ml. For Gram‐positive bacteria with MIC values of 0.5 μg/kg, only SC and PO administration at a dosage of 5 mg/kg showed to be efficacious. MIC ‐based PK / PD analysis by Monte Carlo simulation indicates that the proposed dose regimens of LFX , 5 and 7.5 mg/kg/24 hr by SC route and 10 mg/kg/24 hr by oral route, in dogs may be adequate to recommend as an empirical therapy against S. aureus strains with MIC ≤ 0.5 μg/ml and E. coli strains with MIC values ≤0.125 μg/ml.