Individualised Dosing of Amikacin in Neonates: A Pharmacokinetic/Pharmacodynamic Analysis

Document Type

Article

Publication Date

7-2009

Abstract

PURPOSE:

To examine the pharmacokinetics of amikacin and its pharmacokinetic pharmacodynamic (PKPD) relationship in neonates. To develop an alternative dosing strategy for amikacin in neonates.

METHODS:

A 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.

RESULTS:

The 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.

CONCLUSION:

Simulation 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.

DOI

10.1007/s00228-009-0637-4

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