Pharmacokinetics of levofloxacin after single intravenous, oral and subcutaneous administration to dogs

Abstract

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\xa0mg/kg, respectively. After intravenous administration, distribution was rapid (T½dist 0.127\xa0±\xa00.055\xa0hr) and wide as reflected by the volume of distribution of 1.20\xa0±\xa00.13\xa0L/kg. Drug elimination was relatively slow with a total body clearance of 0.11\xa0±\xa00.03\xa0L\xa0kg-1 \xa0hr-1 and a T½ for this process of 7.85\xa0±\xa02.30\xa0hr. After oral and subcutaneous administration, absorption half-life and Tmax were 0.35 and 0.80\xa0hr and 1.82 and 2.82\xa0hr, respectively. The bioavailability was significantly higher (p\xa0˂\xa00.05) after subcutaneous than oral administration (79.90 vs. 60.94%). No statistically significant differences were observed between other pharmacokinetic parameters. Considering the AUC24\xa0hr /MIC and Cmax /MIC ratios obtained, it can be concluded that LFX administered intravenously (2.5\xa0mg/kg), subcutaneously (5\xa0mg/kg) or orally (5\xa0mg/kg) is efficacious against Gram-negative bacteria with MIC values of 0.1\xa0μg/ml. For Gram-positive bacteria with MIC values of 0.5\xa0μg/kg, only SC and PO administration at a dosage of 5\xa0mg/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\xa0mg/kg/24\xa0hr by SC route and 10\xa0mg/kg/24\xa0hr by oral route, in dogs may be adequate to recommend as an empirical therapy against S.\xa0aureus strains with MIC\xa0≤\xa00.5\xa0μg/ml and E.\xa0coli strains with MIC values ≤0.125\xa0μg/ml.