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Population Pharmacokinetics of Gentamicin in Neonates Using a Nonlinear, Mixed‐Effects Model
Author(s) -
Jensen Paul D.,
Edgren Bruce E.,
Brundage Richard C.
Publication year - 1992
Publication title -
pharmacotherapy: the journal of human pharmacology and drug therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.227
H-Index - 109
eISSN - 1875-9114
pISSN - 0277-0008
DOI - 10.1002/j.1875-9114.1992.tb04506.x
Subject(s) - nonmem , pharmacokinetics , population , volume of distribution , population pharmacokinetics , medicine , distribution (mathematics) , statistics , mathematics , pharmacology , environmental health , mathematical analysis
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.