Pharmacokinetics of Amikacin after a Single Intravenous Dose

Abstract

Amikacin, an aminoglycoside antibiotic, has been used extensively in humans and other animals to treat infections produced by Gram-negative bacteria. The pharmacokinetics of amikacin has been studied in foals, but because of its high cost it has not been studied in adult horses. The present study was designed to determine if a single intravenous dose of amikacin (10 mg/kg) will reach therapeutic concentrations in plasma of adult horses (n=6) and to evaluate the concentration of amikacin in synovial, peritoneal, and interstitial fluid with the same dosage. Serum concentrations of amikacin averaged 115.93 ± 8.254 μg/ml at three minutes, and after 60 minutes the mean concentration was 39.311 ± 5.052 μg/ml. The area under the curve (AUC) was 139.34 ± 34.02 μg*h/ml; the elimination half-life (t½β) was 1.346 ± 0.4 hours; the total body clearance was 1.251 ± 0.281 ml/min/kg, and the mean residual time (MRT) was 1.814 ± 0.5 hours. The concentration of amikacin in serum for all horses was below the minimum detectable concentration for the assay used at 24 hours. The mean maximum concentration (Cmax) of amikacin after a single intravenous injection was 19.78 ± 7.14 μg/ml and 21.44 ± 4.39 μg/ml for synovial and peritoneal fluid, respectively. The time to achieve maximum concentration (Tmax) was 65 ± 12.24 minutes for synovial fluid and 115 ± 12.24 minutes for peritoneal fluid. The area under the curve to the infinite (AUC0-∞) was 100.02 ± 39.89 μg*h/ml for synovial and 139.99 ± 25.88 μg*h/ml for peritoneal fluid. Amikacin in the interstitial fluid reached a mean Cmax of 10.82 ± 5.33 μg/ml, and after 24 hours the mean concentration was 3.316 ± 1.69 μg/ml. Based on the results of the pharmacokinetic analysis, it will appear that a single dose of amikacin (10 mg/kg) in adult horses would be therapeutic in infections caused by susceptible bacteria with a minimum inhibitory concentration (MIC) of ≤8 μg/ml. Due to individual variation, close drug monitoring is recommended.