A Population Pharmacokinetic Model for Vancomycin in Pediatric Patients and Its Predictive Value in a Naive Population

Abstract

The objectives of this study were to (i) construct a population pharmacokinetic (PK) model able to describe vancomycin (VAN) concentrations in serum in pediatric patients, (ii) determine VAN PK parameters in this population, and (iii) validate the predictive ability of this model in a naive pediatric population. Data used in this study were obtained from 78 pediatric patients (under 18 years old). PK analyses were performed using compartmental methods. The most appropriate model was chosen based on the evaluation of pertinent graphics and calculation of the Akaike information criterion test. The population PK analysis was performed using an iterative two-stage method. A two-compartment PK model using age, sex, weight, and serum creatinine as covariates was determined to be the most appropriate one to describe serum VAN concentrations. The quality of fit was very good, and the distribution of weighted residuals was found to be homoscedastic (Wilcoxon signed rank test). There has been a major increase in the clinical use of vancomycin (VAN) in the last 20 years. This may be partly due to the increased and prolonged use of intravenous lines (Hickman catheters, etc.) and to the development of aggressive immunosuppressive therapies. This increase in the utilization of VAN may be responsible for the clinical emergence of enterococcal (3) and staphylococcal (8) strains resistant to this drug (1). It is therefore crucial for clinicians to use this antibiotic in a more rational manner.Monitoring serum VAN concentrations is still a subject of controversy. Administration of doses to pediatric patients that are based only on body weight have frequently been associated with inappropriate concentrations (10, 14). Some authors have therefore suggested utilizing demographic data (such as age, sex, and height) as well as the patient's estimated renal function in order to attain desired concentrations in serum in the majority of their treated patients (2).Little is known about the pharmacokinetics (PK) of VAN in children and adolescents. In fact, only one detailed PK study involving 18 patients in that age group has been published (16). We propose to improve the PK knowledge of VAN in pediatric patients. The objectives of this study are (i) to construct a population PK model able to describe serum VAN concentrations, (ii) to determine VAN PK parameters in a pediatric population, and (iii) to validate the predictive ability of this PK model in a naive pediatric population, using Bayesian adaptive control. MATERIALS AND METHODSWe used, retrospectively, a data bank consisting of 98 patients who received VAN therapy. This bank was compiled by the clinical pharmacists of our center, between January 1994 and July 1996. Patients with at least one available serum creatinine value and one set of peak and trough VAN serum concentrations were included in the study (78 out of 98 patients). Age, weight, sex, and serum creatinine data were available for each subject and are summarized in Table 1. Data collected concerning VAN therapy included ...

Population Pharmacokinetics and Dosing Optimization of Vancomycin in Children with Malignant Hematological Disease

“…In children, the standard dose evaluation studies of antimicrobials are usually based on a "nonselected" pediatric population and do not take into account the potential impact of the disease and disease state, which are the main factors that ultimately influence drug exposure in the clinical setting (17). For the purposes of comparison, the demographics and pharmacokinetic parameters of vancomycin obtained from different pediatric studies (10,18,19) are summarized in Table 4. The magnitude of the differences provides strong argument for studying pharmacokinetics in selected subgroups of patients.…”

Evaluation of Target Attainment of Vancomycin Area Under the Curve in Children With Methicillin-Resistant Staphylococcus Aureus Bacteremia

“…Using a validated pediatric pharmacokinetic model for vancomycin[14],[manuscript pending review], sparse sampling with Bayesian estimation was used to calculate AUC 24h .…”

Validation of a Pediatric Population Pharmacokinetic Model for Vancomycin

“…With that said, we found there was no significant difference in precision and bias between the Lamarre validation data and our validation results. 12 Therefore we feel that this pediatric population PK model for vancomycin with Bayesian estimation can be used in a general pediatric population to reliably predict AUC.…”

“…12; 13 The model covariates included age, weight, and serum creatinine. Population parameters and their distributions were defined as means (± standard deviation) and are shown in Table 1.…”