Determination of population pharmacokinetic parameters for amikacin in neonates using mixed-effect models.
OBJECTIVE
The population pharmacokinetics of amikacin, in neonates, was investigated using the nonlinear mixed effects model (NONMEM).


METHODS
One hundred and six steady-state amikacin serum levels were obtained from 53 black neonates with a mean gestational age of 35.1 weeks and mean age at the start of treatment of 3.1 days. A one-compartment model was used to fit the data.


RESULTS
The final models for clearance (CL) and volume of distribution (V) were: CL(l.h(-1)) = 0.031WT(1.45) x P and V(l) = 0.316WT(1.44) where WT = birth weight (kg) and P = 1.28 for girls and 1.0 for boys. Inclusion of other fixed effect parameters in the model did not significantly improve the fit of the data. The inter-individual variability for CL and V were 18% and 13%. respectively. Intra-individual variability was 29%. Mean (95% CI) values of CL, V and half-life were 0.048 (0.045, 0.051) l.h(-1).kg(-1), 0.434 (0.414, 0.453) l.kg(-1) and 6.4 (6.2, 6.6) h respectively.


CONCLUSIONS
Birth weight was an important determinant of both CL and V and, in this data set, gender was also found to influence CL. Mean population pharmacokinetic values were within the range of those previously derived for other neonatal populations using traditional methods.
Botha
J H
JH
Department of Experimental and Clinical Pharmacology, Medical School, Congella, Republic of South Africa. botha@med.und.ac.za
du Preez
M J
MJ
Miller
R
R
Adhikari
M
M
D000583:Amikacin / Q000493:pharmacokinetics*; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D044383:Black People; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008657:Metabolic Clearance Rate; D015233:Models, Statistical; D012737:Sex Factors
D000900:Anti-Bacterial Agents; D000583:Amikacin