Effect of age on the pharmacokinetics of a single daily dose of gentamicin sulfate in healthy foals

Abstract

Reasons for performing study: Therapeutic drug monitoring in a small number of foals of various ages indicates that the standard adult dose of 6.6mg/kg bwt q. 24h for gentamicin is too low and a dose of 12mg/kg bwt has been proposed. The pharmacokinetics of this dosage in foals and the ages at which this higher dose should be used have not previously been investigated. Objective: To determine the effect of age on the pharmacokinetics of a single 12mg/kg bwt i.v. dose of gentamicin in foals. Methods: Six healthy foals were given a single i.v. dose of gentamicin at 1-3 days, 2, 4, 8 and 12 weeks of age. Plasma concentrations were measured using LC-MS/MS. Results: Elimination half-life (mean ± s.d.) was significantly longer in 1-3-day-old foals (8.2 ± 2.0h) than in foals 4 weeks of age (3.7 ± 1.5h) or older. Volume of distribution was significantly higher in 1-3-day-old foals (0.75 ± 0.20l/kg bwt) than in 8- (0.27 ± 0.10l/kg bwt) or 12-week-old foals (0.29 ± 0.11l/kg bwt). Concentrations of gentamicin 1 h after administration were significantly lower in 1-3-day-old foals (20.52 ± 2.07μg/ml) than in all other age groups (>42.16 ± 17.57μg/ml). Concentrations of gentamicin 24h after administration were significantly higher in the 1-3-day-old foals (1.97 ± 0.90μg/ml) than in all the other age groups (<0.85 ± 0.46μg/ml). Conclusions: The pharmacokinetics of gentamicin change considerably in the first 2 weeks of life. Potential relevance: Intravenous administration of gentamicin at a dose of 12mg/kg bwt q. 36h would be required in foals less than 2 weeks of age. In foals 2 weeks of age or older, a lower dose of 6.6mg/kg bwt given q. 24h was predicted to be adequate. © 2012 EVJ Ltd.