Pharmacokinetics of a single bolus intravenous, intramuscular and subcutaneous dose of disodium fosfomycin in horses.

This study investigates the effectiveness and absorption rate (pharmacokinetics) of the antibiotic disodium fosfomycin in horses. It was administered at different doses and via different routes (intravenously, intramuscularly, and subcutaneously). The findings suggest effective concentrations of the antibiotic could be maintained in the bloodstream for up to 10 hours following a subcutaneous dose of 20 mg/kg.

Research Methodology

• The research revolved around disodium fosfomycin, an antibiotic, and its pharmacokinetics (the absorption, distribution, metabolism, and excretion of the drug) in horses.
• The horse subjects were administered with 10 mg/kg and 20 mg/kg of disodium fosfomycin through three different routes: intravenously (IV), intramuscularly (IM), and subcutaneously (SC).
• The pharmacokinetic properties such as serum concentration at time zero (C(S0)), the maximum serum concentration (Cmax), and area under the curve AUC(0-12)/MIC(90) ratio were determined and compared after administering the drug through each route.

Results and Findings

• At time zero, the serum concentration was recorded as 112.21 microg/mL for the 10 mg/kg dose and 201.43 microg/mL for the 20 mg/kg dose.
• The absorbed percentage of the total drug administered–bioavailability–after subcutaneous administration was 84% and 86% for the 10 mg/kg and 20 mg/kg dose respectively.
• When the sensitivity of bacteria to fosfomycin was considered, the maximum serum concentration obtained was 56.14 microg/mL with the 10 mg/kg SC dose and increased to 72.14 microg/mL with the 20 mg/kg SC dose.
• The researchers concluded that administering 20 mg/kg SC could provide clinically effective plasma concentrations for up to 10 hours, considering fosfomycin’s time-dependent antimicrobial properties.
• Assuming a 12-hour dosing interval, another indicator of efficacy is the AUC(0-12)/MIC(90) ratio. The study calculated the ratios as 996 and 1260 for the 10mg/kg and 20mg/kg doses respectively when administered to bacteria sensitive to fosfomycin.
• The AUC(0-12)/MIC(90) ratio decreases significantly to 15 and 19 for the 10 mg/kg and 20 mg/kg doses respectively when considering a more resistant strain of bacteria.

Conclusive Statement

• This research suggests that the antibiotic disodium fosfomycin, when administered subcutaneously at a dose of 20 mg/kg, can maintain effective concentrations in the bloodstream of horses for up to 10 hours.
• The implications of this study could influence dosage and administration protocol for this antibiotic in equine veterinary practice, particularly for managing infections by fosfomycin-sensitive bacteria.