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

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, i.v., 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 microg/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 microg/mL; area under the curve (AUC) was 293.0 +/- 61.0, 202.3 +/- 40.4, and 180.9 +/- 31.2 (microg x h)/mL; elimination half-life (t(1/2)beta) 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 x kg), respectively. There were significant increases in clearance and decreases in t(1/2)beta, 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.