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

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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.

Original languageEnglish (US)
Pages (from-to)473-479
Number of pages7
JournalAmerican Journal of Veterinary Research
Volume65
Issue number4
DOIs
StatePublished - Apr 2004

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amikacin
Amikacin
foals
pharmacokinetics
Pharmacokinetics
dosage
Area Under Curve
Newborn Animals
renal function
half life
Half-Life
Parturition
Kidney
kinetics

ASJC Scopus subject areas

  • veterinary(all)

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Pharmacokinetics of a high dose of amikacin administered at extended intervals to neonatal foals. / Magdesian, K G; Wilson, William D; Mihalyi, Judy.

In: American Journal of Veterinary Research, Vol. 65, No. 4, 04.2004, p. 473-479.

Research output: Contribution to journalArticle

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title = "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.",
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AB - 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.

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