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 6.6 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. OBJECTIVE: To determine the effect of age on the pharmacokinetics of a single 12 mg/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 &#xb1; s.d.) was significantly longer in 1-3-day-old foals (8.2 &#xb1; 2.0 h) than in foals 4 weeks of age (3.7 &#xb1; 1.5 h) or older. Volume of distribution was significantly higher in 1-3-day-old foals (0.75 &#xb1; 0.20 l/kg bwt) than in 8- (0.27 &#xb1; 0.10 l/kg bwt) or 12-week-old foals (0.29 &#xb1; 0.11 l/kg bwt). Concentrations of gentamicin 1 h after administration were significantly lower in 1-3-day-old foals (20.52 &#xb1; 2.07 &#x3bc;g/ml) than in all other age groups (>42.16 &#xb1; 17.57 &#x3bc;g/ml). Concentrations of gentamicin 24 h after administration were significantly higher in the 1-3-day-old foals (1.97 &#xb1; 0.90 &#x3bc;g/ml) than in all the other age groups (<0.85 &#xb1; 0.46 &#x3bc;g/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 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.