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8/10/2019 Antimicrob. Agents Chemother.-2000-Lamarre-278-82.pdf
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10.1128/AAC.44.2.278-282.2000.
2000, 44(2):278. DOI:Antimicrob. Agents Chemother.Patrice Lamarre, Denis Lebel and Murray P. Ducharme
Predictive Value in a Naive PopulationVancomycin in Pediatric Patients and ItsA Population Pharmacokinetic Model for
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ANTIMICROBIALAGENTS ANDCHEMOTHERAPY,0066-4804/00/$04.000
Feb. 2000, p. 278282 Vol. 44, No. 2
Copyright 2000, American Society for Microbiology. All Rights Reserved.
A Population Pharmacokinetic Model for Vancomycin in PediatricPatients and Its Predictive Value in a Naive Population
PATRICE LAMARRE,1,2 DENIS LEBEL,2 ANDMURRAY P. DUCHARME1*
Faculte de Pharmacie, Universite de Montreal,1 and Departement de Pharmacie,Hopital Ste-Justine,2 Montreal, Canada
Received 9 April 1999/Returned for modification 21 July 1999/Accepted 1 November 1999
The objectives of this study were to (i) construct a population pharmacokinetic (PK) model able to describevancomycin (VAN) concentrations in serum in pediatric patients, (ii) determine VAN PK parameters in thispopulation, and (iii) validate the predictive ability of this model in a naive pediatric population. Data used inthis study were obtained from 78 pediatric patients (under 18 years old). PK analyses were performed usingcompartmental methods. The most appropriate model was chosen based on the evaluation of pertinent graph-ics and calculation of the Akaike information criterion test. The population PK analysis was performed usingan iterative two-stage method. A two-compartment PK model using age, sex, weight, and serum creatinine ascovariates was determined to be the most appropriate one to describe serum VAN concentrations. The qualityof fit was very good, and the distribution of weighted residuals was found to be homoscedastic (Wilcoxon signed
rank test). Fitted population PK parameters (mean standard deviation) were as follows: central clearance(0.1 0.05 liter/h/kg), central volume of distribution (0.27 0.07 liter/kg), peripheral volume of distribution(0.16 0.07 liter/kg), and distributional clearance (0.16 0.07 liter/kg). The predictive ability of the developedmodel (including the above-mentioned covariates) was evaluated in a naive population of 19 pediatric patients.The predictability was very good. Precision (95% confidence interval [CI]) (peak, 4.1 [1.4], and trough, 2.2[0.7]) and bias (95% CI) (peak, 0.58 [2.2], and trough, 0.63 [1.1] mg/liter) were significantly (P
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