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Vancomycin AUC0-24 estimation using first-order pharmacokinetic methods in pediatric patients.
Hope H Brandon1, David S Burgess2, Katie L Wallace1,2
1Department of Pharmacy, University of Kentucky HealthCare, Lexington, Kentucky, USA.
Pharmacotherapy
|March 27, 2024
Summary
Vancomycin dosing in children needs better monitoring. This study shows minimum concentration (Cmin) is a poor predictor of therapeutic area under the curve (AUC0-24), supporting AUC-based vancomycin monitoring in pediatrics.
Area of Science:
- Pharmacokinetics and Pharmacodynamics
- Pediatric Infectious Diseases
- Drug Dosing and Therapeutic Drug Monitoring
Background:
- Optimal vancomycin dosing and monitoring in pediatric patients remain challenging, with a shift towards area under the curve over 24 hours (AUC0-24) over minimum concentration (Cmin).
- Limited real-world data exist on the feasibility of using two-concentration kinetics and first-order equations to estimate vancomycin AUC0-24 in pediatric populations.
Purpose of the Study:
- To investigate the relationship between vancomycin dose, AUC0-24, and Cmin.
- To evaluate the utility of first-order equations for estimating vancomycin AUC0-24 across four pediatric age groups.
- To assess the correlation between Cmin and AUC0-24 for vancomycin therapy monitoring in children.
Main Methods:
- Retrospective cohort study of pediatric patients (<18 years) receiving intravenous vancomycin (2020-2022).
- Inclusion criteria: ≥24 hours of vancomycin therapy with two concentrations obtained within 96 hours; exclusion of patients with baseline renal dysfunction.
- Patients categorized into four age groups: neonates, infants, children, and adolescents; pharmacokinetic parameters and AUC0-24 estimated using first-order equations.
Main Results:
- 219 pediatric patients analyzed; median age 6 years. Vancomycin daily doses varied by age group.
- Median Cmin was 8.68 mg/L and median AUC0-24 was 505 mg*h/L. More supratherapeutic than subtherapeutic AUC0-24 values were observed.
- Suboptimal correlation between Cmin and AUC0-24 noted; 71% of patients with Cmin 5-10 mg/L had therapeutic AUC0-24. 92% of supratherapeutic AUC0-24 cases had Cmin ≥15 mg/L. 10% experienced acute kidney injury.
Conclusions:
- First-order equations are feasible for estimating vancomycin AUC0-24 in pediatric patients using two steady-state concentrations.
- The suboptimal correlation between AUC0-24 and Cmin indicates Cmin is not a reliable surrogate for therapeutic AUC0-24 in pediatrics.
- Recommend AUC0-24 monitoring for vancomycin efficacy and safety in pediatric patients, aligning with current guidelines.
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