Individualised Dosing of Amikacin in Neonates: A Pharmacokinetic/Pharmacodynamic Analysis
To examine the pharmacokinetics of amikacin and its pharmacokinetic pharmacodynamic (PKPD) relationship in neonates. To develop an alternative dosing strategy for amikacin in neonates.
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.
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.
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.
Sherwin, C. M.,
Van Der Linden, A.,
Medlicott, N. J.,
& Reith, D.
(2009). Individualised Dosing of Amikacin in Neonates: A Pharmacokinetic/Pharmacodynamic Analysis. European Journal of Clinical Pharmacology, 65 (7), 705-713.