Population Pharmacokinetics of Gentamicin in Neonates Using a Nonlinear, Mixed‐Effects Model

Abstract

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.