Bayesian Estimation of Vancomycin Pharmacokinetics in Obese Children: Matched Case-Control Study
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Published on: March 3, 2023
Jennifer Le1, Edmund V Capparelli2, Uzra Wahid2
1University of California, San Diego, Skaggs School of Pharmacy and Pharmaceutical Sciences and School of Medicine, La Jolla, California; Miller Children׳s Hospital of Long Beach, Long Beach, California.
Insights
Actual and allometric weight are practical for estimating vancomycin volume of distribution (Vd) and clearance (CL) in obese children. However, these pharmacokinetic differences are minor and unlikely to impact vancomycin dosing adjustments.
Area of Science:
- Pharmacology
- Pediatrics
- Clinical Pharmacokinetics
Background:
- Vancomycin is a critical antibiotic for treating serious Gram-positive infections in children.
- Accurate estimation of vancomycin's pharmacokinetic parameters, including volume of distribution (Vd) and clearance (CL), is essential for optimizing therapeutic efficacy and minimizing toxicity.
- Body size descriptors significantly influence pharmacokinetic variability, particularly in pediatric populations with diverse body compositions.
Purpose of the Study:
- To compare various body size descriptors for their effectiveness in estimating vancomycin Vd and CL in pediatric patients.
- To determine if actual weight and allometric weight (weight^0.75) are suitable for predicting vancomycin Vd and CL in obese versus normal-weight children.
Main Methods:
- A matched case-control study involving pediatric patients (3 months to 21 years) who received vancomycin for at least 48 hours.
- Cases were defined as individuals with a body mass index (BMI) in the ≥85th percentile, while controls were nonobese individuals matched for age and baseline serum creatinine (SCr).
- A one-compartment model with first-order kinetics was employed to estimate individual Vd and CL using Bayesian post hoc analysis.
Main Results:
- The study included 87 matched pairs, with 389 vancomycin serum concentrations analyzed.
- Obese children (cases) had significantly higher median weights (44.0 kg) compared to normal-weight children (controls, 31.3 kg), with similar age and baseline SCr levels.
- Actual weight and allometric weight were utilized in the final model; mean Vd and CL were marginally lower in cases (obese) than controls, with differences of 0.012 L/kg and 0.014 L/kg/h, respectively.
Conclusions:
- Actual weight and allometric weight serve as convenient and reasonable surrogates for body fat in estimating vancomycin Vd and CL in obese pediatric patients.
- Despite observed pharmacokinetic differences, the magnitude of variation in Vd and CL between obese and normal-weight children is small.
- These minor pharmacokinetic differences are unlikely to necessitate significant adjustments in vancomycin dosing strategies for clinical practice.
Purpose:
The study objective was to compare different body size descriptors that best estimate vancomycin Vd and clearance (CL).
Methods:
Patients between 3 months and 21 years old who received vancomycin for ≥48 hours from 2003 to 2011 were evaluated in this matched case-control study. Cases had body mass index in the ≥85th percentile; controls were nonobese individuals who were matched by age and baseline serum creatinine (SCr). Using a 1-compartment model with first-order kinetics, Bayesian post hoc individual Vd and CL were estimated.
Findings:
Analysis included 87 matched pairs with 389 vancomycin serum concentrations. Median ages were 10.0 (interquartile range [IQR], 4.8-15.2) years for cases (overweight and obese children) and 10.2 (IQR, 4.5-14.8) years for controls (normal-weight children). Median weights were 44.0 (IQR, 23.4-78.1) kg for cases and 31.3 (IQR, 16.8-47.1) kg for controls. Mean (SD) for the baseline SCr values were also similar between the groups: 0.51 (0.22) (IQR, 0.34-0.67) mg/dL and 0.48 (0.20) (IQR, 0.30-0.60) mg/dL for the cases and controls, respectively. Actual weight and allometric weight (ie, weight(0.75)) were used in the final model to estimate Vd and CL, respectively. The mean Vd and CL, based on weight, for cases were lower than controls by 0.012 L/kg and 0.014 L/kg/h, respectively.
Implications:
In obese children, actual weight and allometric weight are reasonable, convenient estimations of body fat to use for estimating vancomycin Vd and CL, respectively. However, these pharmacokinetic differences between obese children and those with normal weights are small and may not likely to be clinically relevant in dose variation.
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