Pharmacokinetics of amikacin in plasma and selected body fluids of healthy horses after a single intravenous dose.

Reasons For Performing Study: No studies have determined the pharmacokinetics of low-dose amikacin in the mature horse.

Objectives: To determine if a single i.v. dose of amikacin (10 mg/kg bwt) will reach therapeutic concentrations in plasma, synovial, peritoneal and interstitial fluid of mature horses (n=6).

Methods: Drug concentrations of amikacin were measured across time in mature horses (n=6); plasma, synovial, peritoneal and interstitial fluid were collected after a single i.v. dose of amikacin (10 mg/kg bwt).

Results: The mean±s.d. of selected parameters were: extrapolated plasma concentration of amikacin at time zero 144±21.8 µg/ml; extrapolated plasma concentration for the elimination phase 67.8±7.44 µg/ml, area under the curve 139±34.0 µg*h/ml, elimination half-life 1.34±0.408 h, total body clearance 1.25±0.281 ml/min/kg bwt; and mean residence time (MRT) 1.81±0.561 h. At 24 h, the plasma concentration of amikacin for all horses was below the minimum detectable concentration for the assay. Selected parameters in synovial and peritoneal fluid were maximum concentration (Cmax) 19.7±7.14 µg/ml and 21.4±4.39 µg/ml and time to maximum concentration 65±12.2 min and 115±12.2 min, respectively. Amikacin in the interstitial fluid reached a mean peak concentration of 12.7±5.34 µg/ml and after 24 h the mean concentration was 3.31±1.69 µg/ml. Based on a minimal inhibitory concentration (MIC) of 4 µg/ml, the mean Cmax:MIC ratio was 16.9±1.80 in plasma, 4.95±1.78 in synovial fluid, 5.36±1.10 in peritoneal fluid and 3.18±1.33 in interstitial fluid.

Conclusions: Amikacin dosed at 10 mg/kg bwt i.v. once a day in mature horses is anticipated to be effective for treatment of infection caused by most Gram-negative bacteria.

Potential Relevance: Low dose amikacin (10 mg/kg bwt) administered once a day in mature horses may be efficacious against susceptible microorganisms.