Population pharmacokinetics of gentamicin in neonates using a nonlinear, mixed-effects model.
The population pharmacokinetics of gentamicin in neonates was determined using a nonlinear, mixed-effects model (NONMEM). The final regression equations derived to estimate clearance (Cl) and volume of distribution (Vd) were Cl = 0.120 * (WT/2.4)1.36 L/hr and Vd = 0.429 * (WT) L. The interindividual variability (% CV) for clearance was 26.2% and for volume of distribution 15.9%. Intraindividual variability was 11.0%. In a separate group of 30 neonates, the predictive ability of the NONMEM-generated population variables was compared to the predictions from a standard two-stage population analysis. The trough concentrations predicted using NONMEM-generated parameters were significantly less biased and more precise; there were no significant differences between the methods in predicting peaks. NONMEM is a useful tool for determining population pharmacokinetics and appears to be consistent across populations using routine clinical data and limited observation.
Jensen
P D
PD
Department of Pharmacy, Children's Hospital of St. Paul, Minnesota 55102.
Edgren
B E
BE
Brundage
R C
RC
D005839:Gentamicins / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016905:Gram-Negative Bacterial Infections / Q000517:prevention & control; D006801:Humans; D007231:Infant, Newborn; D008657:Metabolic Clearance Rate; D015233:Models, Statistical; D012044:Regression Analysis; D015203:Reproducibility of Results
D005839:Gentamicins