Pharmacokinetics of Once‐Daily Amikacin in Healthy Foals and Therapeutic Drug Monitoring in Hospitalized Equine Neonates

Abstract

The objectives of this study were to investigate the pharmacokinetics of once‐daily amikacin in healthy neonates, to determine amikacin concentrations in hospitalized foals, and to determine the minimum inhibitory concentrations (MICs) of amikacin against gram‐negative isolates from blood cultures in septic foals. Median half‐life, clearance, and volume of distribution of amikacin in healthy 2‐ to 3‐day‐old foals after administration of an intravenous bolus of amikacin (25 mg/kg) were 5.07 hours (4.86‐5.45 hours), 1.82 mL/min/kg (1.35‐1.97 mL/min/kg), and 0.785 L/kg (0.638‐0.862 L/kg), respectively. Statistically significant (P<.05) decreases in area under the curve (14% decrease), mean residence time (19% decrease), and C24hplasma amikacin concentrations (29% decrease) occurred between days 2–3 and 10–11. Plasma amikacin concentrations in healthy foals at 0.5 hours (C05h) were significantly higher (P= .02) than those of hospitalized foals. Sepsis, prematurity, and hypoxemia did not alter amikacin concentrations. The MIC at which 90% of all gram‐negative isolates from equine neonatal blood cultures were inhibited by amikacin was 4 |xg/mL, suggesting that amikacin C05hof 40 μg/mL should be targeted to achieve a maximum serum concentration to MIC ratio of 10:1. The proportion of foals with C05h>40 μg/mL was significantly higher(P<.0001) in hospitalized foals receiving a dose of amikacin at 25 mg/kg (22/24 or 92%) than in foals receiving a dose at 21 mg/kg (9/25 or 36%), whereas no difference was found in the proportion of foals with C24hconcentrations ≥3 μg/mL between the 2 groups. An initial dose at 25 mg/kg is recommended for once‐daily amikacin in equine neonates.