Pharmacokinetics/pharmacodynamics cut-off determination for fosfomycin using Monte Carlo simulation in healthy horses.

This research investigated the pharmacokinetics and pharmacodynamics of Fosfomycin in horses, to determine the cut-off for the drug to be considered effective against E.Coli. This measurement was made through Monte Carlo simulations following the introduction of the drug via intravenous administration.

Understanding the Objective

• The primary objective of the study was to determine the pharmacokinetics/pharmacodynamics (PK/PD) cut-off for Fosfomycin (FOM), a veterinary antibiotic, in horses.
• The cut-off is defined as the minimal inhibitory concentration (MIC) of the drug required to have a 90% probability of achieving a PK/PD target, in this case, determined by a specific Area Under the free plasma concentration-time curve (AUC/MIC ratio) which was set to >24hr.

The Methodology

• A group of nine healthy horses were administered a single intravenous dose of Fosfomycin, with drug concentrations being subsequently monitored using liquid chromatography/mass spectrometry.
• The resulting data was modeled using a nonlinear mixed-effects model, which was then subject to Monte Carlo simulation. This kind of simulation, based on repeated random sampling, is a statistical technique widely used to understand the influence of risk and uncertainty in prediction and forecasting models.
• The PK/PD cut-off was determined based on the MIC value which provides a 90% chance of achieving the PK/PD target.

The Findings

• The researchers determined that a dosage regimen of 20 mg/kg body weight of Fosfomycin, administered intravenously every 12 hours, was effective against E.coli in healthy horses when the MIC value is ≤16.0 mg/L.
• This conclusion is based on the cut-off calculation and the actual MIC values found in the wild population of E.coli.

Implications of the Findings

• Based on the study, it is suggested that veterinarians use Fosfomycin with a dosage of 20 mg/kg every 12 hours for treating E.coli infections in horses, provided the MIC is under 16 µg/mL.
• This research therefore provides valuable dosage information for the effective use of Fosfomycin in veterinary medicine, while also highlighting the potential relevance of the drug to human health.