Pharmacokinetics of tobramycin following intravenous, intramuscular, and intra-articular administration in healthy horses.

The research article explores the pharmacokinetics (movement of the drug within the body) of tobramycin, a type of antibiotic, administered using different routes in horses. The study uses a three-way crossover design to indicate how the volume of distribution, clearance, and half-life of tobramycin differ based on the method of administration, and calculates the bioavailability of the drug in each case.

Methodology

• The researchers introduced the drug to six mares in three different ways and in the following order: intravenous (IV), intramuscular (IM), and combined intravenous and intra-articular (IV+IA).
• The dose for each administration was 4mg/kg.
• Each administration was followed by a washout period of 7 days to ensure the drug was eliminated from their systems before the next administration.
• The researchers measured the maximum plasma concentration (Cmax), the time it took for Cmax to be attained, and the bioavailability post-IM administration.
• Additionally, they also assessed the tolerance level of the mares towards the IM administration of the drug.
• Lastly, six additional mares received an intra-articular administration of the drug. Synovial fluid concentrations were subsequently measured to determine drug persistence.

Findings

• An IV administration of the drug results in a volume of distribution, clearance, and half-life of 0.18±0.04 L/kg, 1.18±0.32 mL·kg/min, and 4.61±1.10 h respectively.
• The researchers found that concurrent IA administration did not have any notable effect on the IV pharmacokinetics of tobramycin.
• After an IM administration, the mean maximum plasma concentration (Cmax) was 18.24±9.23μg/mL at 1.0 h, with a regarding bioavailability of 81.22±44.05%.
• Post administration, all drug concentrations at 24h were below 2 μg/mL for all routes. Particularly, trough concentrations at 24 h were 0.04±0.01 μg/mL for the IV and IV/IA routes, and 0.02±0.02 for the IM route.
• An IA administration of 240mg tobramycin resulted in synovial fluid concentrations of 3056.47±1310.89μg/mL that persisted for up to 48h with concentrations of 14.80±7.47μg/mL.
• It was observed that administering tobramycin using an intra-articular route caused a slight increase in synovial fluid cell count, indicating a mild case of chemical synovitis. Despite this, the method proved to be safe for administration.
• Monte Carlo simulations were performed to predict the antibiotic efficacy of tobramycin against bacteria with different minimum inhibitory concentrations (MICs). The results suggest that tobramycin would be effective against bacteria with a MIC of 2 μg/mL for IV administration and 1 μg/mL for IM administration.