title: 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 C24h plasma amikacin concentrations (29% decrease) occurred between days 2-3 and 10-11. Plasma amikacin concentrations in healthy foals at 0.5 hours (C0.5h) 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 microg/mL, suggesting that amikacin C0.5h of 40 microg/mL should be targeted to achieve a maximum serum concentration to MIC ratio of 10:1. The proportion of foals with C0.5h 40 microg/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 C24h concentrations > or = 3 microg/mL between the 2 groups. An initial dose at 25 mg/kg is recommended for once-daily amikacin in equine neonates.
authors.affiliation: Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL 32610, USA.
authors.forename: Erica Paige
authors.initials: EP
authors.lastname: Bucki
authors.forename: Steeve
authors.initials: S
authors.lastname: Giguère
authors.forename: Margo
authors.initials: M
authors.lastname: Macpherson
authors.forename: Rachel
authors.initials: R
authors.lastname: Davis
mesh_terms: D000583:Amikacin / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000818:Animals; D000831:Animals, Newborn; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016470:Bacteremia / Q000188:drug therapy / Q000378:metabolism / Q000662:veterinary*; D005260:Female; D016231:Fluorescence Polarization Immunoassay / Q000662:veterinary; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy / Q000378:metabolism / Q000662:veterinary*; D006207:Half-Life; D006734:Horse Diseases / Q000188:drug therapy / Q000378:metabolism*; D006736:Horses / Q000378:metabolism*; D000860:Hypoxia / Q000378:metabolism / Q000662:veterinary; D008297:Male; D008657:Metabolic Clearance Rate / Q000502:physiology; D008826:Microbial Sensitivity Tests / Q000662:veterinary
chemical_list: D000900:Anti-Bacterial Agents; D000583:Amikacin