EXPERIMENTAL AND BASIC RESEARCH STUDIES
Effect of age on the pharmacokinetics of a single daily dose of gentamicin sulfate in healthy foals
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Reasons for performing study
Therapeutic drug monitoring in a small number of foals of various ages indicates that the standard adult dose of 6.6 mg/kg bwt q. 24 h for gentamicin is too low and a dose of 12 mg/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.
To determine the effect of age on the pharmacokinetics of a single 12 mg/kg bwt i.v. dose of gentamicin in foals.
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.
Elimination half-life (mean ± s.d.) was significantly longer in 1–3-day-old foals (8.2 ± 2.0 h) than in foals 4 weeks of age (3.7 ± 1.5 h) or older. Volume of distribution was significantly higher in 1–3-day-old foals (0.75 ± 0.20 l/kg bwt) than in 8- (0.27 ± 0.10 l/kg bwt) or 12-week-old foals (0.29 ± 0.11 l/kg bwt). Concentrations of gentamicin 1 h after administration were significantly lower in 1–3-day-old foals (20.52 ± 2.07 μg/ml) than in all other age groups (>42.16 ± 17.57 μg/ml). Concentrations of gentamicin 24 h after administration were significantly higher in the 1–3-day-old foals (1.97 ± 0.90 μg/ml) than in all the other age groups (<0.85 ± 0.46 μg/ml).
The pharmacokinetics of gentamicin change considerably in the first 2 weeks of life.
Intravenous administration of gentamicin at a dose of 12 mg/kg bwt q. 36 h would be required in foals less than 2 weeks of age. In foals 2 weeks of age or older, a lower dose of 6.6 mg/kg bwt given q. 24 h was predicted to be adequate.