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 C 24h plasma amikacin concentrations (29% decrease) occurred between days 2-3 and 10-11. Plasma amikacin concentrations in healthy foals at 0.5 hours (C 0.5h) 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 g/mL, suggesting that amikacin C 0.5h of 40 g/mL should be targeted to achieve a maximum serum concentration to MIC ratio of 10:1. The proportion of foals with C 0.5h 40 g/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 C 24h concentrations 3 g/mL between the 2 groups. An initial dose at 25 mg/kg is recommended for once-daily amikacin in equine neonates.

Effect of Dose on Intra‐Articular Amikacin Sulfate Concentrations Following Intravenous Regional Limb Perfusion in Horses

“…Subsequently, a higher peak concentration of amikacin as observed in the middle carpal joint may result in a prolonged PAE and potentially a longer duration of action. The median concentration of amikacin in the middle carpal and metacarpophalangeal joints at 24 hours were still above the MIC of the Gram‐negative isolates from equine neonates (4 μg/mL) …”

“…Caron et al published on the MIC of methicillin resistant S. aureus isolates from horses where the MIC varied from 2 to 32 μg/mL. Another study reported that all Gram‐negative bacterial isolates from equine neonates had an MIC 90 of 4 μg/mL. Orsini et al measured just 6 isolates that had MIC that varied from 0.5 to 128 μg/mL, and finally Erol et al reported that nocardioform actinomycetes had an MIC 90 of 32 μg/mL.…”

Pharmacokinetics of Butorphanol and Evaluation of Physiologic and Behavioral Effects after Intravenous and Intramuscular Administration to Neonatal Foals

“…The high Cl in foals, compared with adults, was an unexpected finding. Usually Cl is reduced in neonates and increases with age, 20–24 but allometry also may be a factor causing a higher Cl owing to lower body weight. Allometric scaling shows that, for some drugs, Cl increases inversely with body weight 25 …”

Effect of emptying the vasculature before performing regional limb perfusion with amikacin in horses

“…This technique has been previously validated in plasma [11] and synovial fluid of horses [12], and several studies have used the same methodology for the measurement of amikacin in blood and synovial fluid [13,14]. Samples were centrifuged at 1700 g for 5 min, the supernatant stored in plastic tubes and frozen at À78°C until analysis.…”