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

1992; Wiley; Volume: 12; Issue: 3 Linguagem: Inglês

10.1002/j.1875-9114.1992.tb04506.x

1875-9114

Paul D. Jensen, Bruce Edgren, Richard C. Brundage,

Drug Transport and Resistance Mechanisms

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 (V d ) were Cl = 0.120 * (WT/2.4) 1,36 L/hr and V d = 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.