Abstract
Objective—To determine disposition kinetics of amikacin in neonatal foals administered high doses at extended intervals.
Animals—7 neonatal foals.
Procedure—Amikacin was administered (21 mg/kg, IV, q 24 h) for 10 days. On days 1, 5, and 10, serial plasma samples were obtained for measurement of amikacin concentrations and determination of pharmacokinetics.
Results—Mean ± SD peak plasma concentrations of amikacin extrapolated to time 0 were 103.1 ± 23.4, 102.9 ± 9.8, and 120.7 ± 17.9 µg/mL on days 1, 5, and 10, respectively. Plasma concentrations at 1 hour were 37.5 ± 6.7, 32.9 ± 2.6, and 30.6 ± 3.5 µg/mL; area under the curve (AUC) was 293.0 ± 61.0, 202.3 ± 40.4, and 180.9 ± 31.2 (µg · h)/mL; elimination half-life (t1/2β) was 5.33, 4.08, and 3.85 hours; and clearance was 1.3 ± 0.3, 1.8 ± 0.4, and 2.0 ± 0.3 mL/(min · kg), respectively. There were significant increases in clearance and decreases in t1/2β, AUC, mean residence time, and plasma concentrations of amikacin at 1, 4, 8, 12, and 24 hours as foals matured.
Conclusions and Clinical Relevance—Once-daily administration of high doses of amikacin to foals resulted in high peak plasma amikacin concentrations, high 1-hour peak concentrations, and large values for AUC, consistent with potentially enhanced bactericidal activity. Age-related findings suggested maturation of renal function during the first 10 days after birth, reflected in enhanced clearance of amikacin. High-dose, extended-interval dosing regimens of amikacin in neonatal foals appear rational, although clinical use remains to be confirmed. (Am J Vet Res 2004;65:473–479)
