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Eur. J. Clin. Pharmacol. · Jul 2009
Individualised dosing of amikacin in neonates: a pharmacokinetic/pharmacodynamic analysis.
- Catherine M T Sherwin, Sofia Svahn, Antje Van der Linden, Roland S Broadbent, Natalie J Medlicott, and David M Reith.
- Division of Clinical Pharmacology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, MLC 6018, Cincinnati, OH 45229-3039, USA. catherine.sherwin@cchmc.org
- Eur. J. Clin. Pharmacol. 2009 Jul 1;65(7):705-13.
PurposeTo examine the pharmacokinetics of amikacin and its pharmacokinetic pharmacodynamic (PKPD) relationship in neonates. To develop an alternative dosing strategy for amikacin in neonates.MethodsA population PKPD analysis was performed using data collected from 80 neonates with gestational ages from 24 to 41 weeks. The final pharmacokinetic model analysed 358 amikacin concentrations. All neonates were > 72 hours postnatal age. Simulations were performed to develop a new dosing strategy.ResultsThe final covariate model was clearance = 0.23 x (current weight/2)(0.691) x (postmenstrual age/40)(3.23) and volume of distribution = 0.957 x (current weight/2)(0.89). Following the logistic regression analysis of treatment failure, new amikacin target concentrations were estimated and used in development of an alternative dosing strategy.ConclusionSimulation of a new dosing regimen yielded the following recommendations: 15 mg/kg at 36-h intervals, 14 mg/kg at 24-h intervals and 15 mg/kg at 24-h intervals for neonates < or = 28 weeks, 29-36 weeks and > or = 37 weeks postmenstrual age respectively.
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