Pharmacokinetics of a high dose of amikacin administered at extended intervals to neonatal foals

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)