Pharmacokinetics of a single bolus intravenous, intramuscular and subcutaneous dose of disodium fosfomycin in horses |
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| Authors: | Zozaya D H Gutiérrez O L Ocampo C L Sumano L H |
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| Institution: | Departamento de Fisiología y Farmacología, Facultad de Medicina Veterinaria y Zootecnia, Universidad Nacional Autónoma de México, Mexico City, Mexico |
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| Abstract: | Pharmacokinetic parameters of fosfomycin were determined in horses after the administration of disodium fosfomycin at 10 mg/kg and 20 mg/kg intravenously (IV), intramuscularly (IM) and subcutaneously (SC) each. Serum concentration at time zero (CS0) was 112.21 ± 1.27 μg/mL and 201.43 ± 1.56 μg/mL for each dose level. Bioavailability after the SC administration was 84 and 86% for the 10 mg/kg and the 20 mg/kg dose respectively. Considering the documented minimum inhibitory concentration (MIC90) range of sensitive bacteria to fosfomycin, the maximum serum concentration (Cmax) obtained (56.14 ± 2.26 μg/mL with 10 mg/kg SC and 72.14 ± 3.04 μg/mL with 20 mg/kg SC) and that fosfomycin is considered a time-dependant antimicrobial, it can be concluded that clinically effective plasma concentrations might be obtained for up to 10 h administering 20 mg/kg SC. An additional predictor of efficacy for this latter dose and route, and considering a 12 h dosing interval, could be area under the curve AUC0-12/MIC90 ratio which in this case was calculated as 996 for the 10 mg/kg dose and 1260 for the 20 mg/kg dose if dealing with sensitive bacteria. If a more resistant strain is considered, the AUC0-12/MIC90 ratio was calculated as 15 for the 10 mg/kg dose and 19 for the 20 mg/kg dose. |
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