Individualised dosing of amikacin in neonates: a pharmacokinetic/pharmacodynamic analysis.
OBJECTIVE
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.


CONCLUSIONS
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
Catherine M T
CM
Division of Clinical Pharmacology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, MLC 6018, Cincinnati, OH 45229-3039, USA. catherine.sherwin@cchmc.org
Svahn
Sofia
S
Van der Linden
Antje
A
Broadbent
Roland S
RS
Medlicott
Natalie J
NJ
Reith
David M
DM
D000583:Amikacin / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000494:pharmacology*; D001835:Body Weight; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005865:Gestational Age; D006801:Humans; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D007234:Infant, Premature; D007262:Infusions, Intravenous; D008598:Menstruation; D008657:Metabolic Clearance Rate; D008954:Models, Biological; D015203:Reproducibility of Results; D012307:Risk Factors; D018805:Sepsis / Q000188:drug therapy*; D013997:Time Factors; D017211:Treatment Failure
D000900:Anti-Bacterial Agents; D000583:Amikacin