Vancomycin AUC0-24 estimation using first-order pharmacokinetic methods in pediatric patients

Abstract

Introduction: The optimal dosing and monitoring of vancomycin in pediatrics is still unknown but has evolved to emphasize area under the curve over 24 h (AUC_0-24) over minimum concentration (C_min) monitoring. Real-world data supporting the feasibility of two-concentration kinetics with first-order equations for the estimation of vancomycin AUC_0-24 in pediatric patients are lacking.

Objectives: To describe the interplay of vancomycin dose, AUC_0-24, and C_min using first-order equations within four pediatric age groups.

Methods: This is a single-center, retrospective cohort study analyzing pediatric patients (<18 years) receiving intravenous vancomycin between 2020 and 2022. Included patients received at least 24 h of intravenous vancomycin with two concentrations obtained within 96 h of therapy initiation. Patients with baseline renal dysfunction were excluded. Patients were divided into four age categories: neonates (≤28 days), infants (29 days to <1 year), children (1-12 years), and adolescents (13-17 years). First-order equations were utilized to estimate pharmacokinetic parameters and AUC_0-24.

Results: Overall, 219 patients (median age of 6 years [IQR 1-12]) met inclusion criteria. The median vancomycin daily dose was 30 mg/kg in neonates, 70 mg/kg in infants and children, and 52 mg/kg in adolescents. Median C_min and AUC_0-24 values among all age groups were 8.68 mg/L and 505 mg * h/L, respectively. For AUC_0-24 values outside of the therapeutic range (400-600 mg * h/L), more values were SUPRAtherapeutic (>600 mg * h/L) than SUBtherapeutic (<400 mg * h/L). The overall trend within our data showed suboptimal correlation between C_min and AUC_0-24. However, 71% of patients with C_min values of 5-10 mg/L had an AUC_0-24 within the therapeutic range of 400-600 mg * h/L, whereas 23 patients (92%) with a SUPRAtherapeutic AUC_0-24 had a C_min value ≥15 mg/L. Approximately 10% of patients experienced acute kidney injury.

Conclusions: Our data describe the relationship between vancomycin dose, C_min, and AUC_0-24 in pediatric patients. We demonstrated the feasibility of using first-order equations to estimate AUC_0-24, using two concentrations obtained at steady state to monitor efficacy and safety in pediatric patients receiving intravenous vancomycin. Our data showed suboptimal correlation between AUC_0-24 and C_min, which indicates that C_min should not be used as a surrogate marker for a therapeutic AUC_0-24 in pediatric patients. In alignment with the 2020 vancomycin consensus guidelines, we suggest utilizing AUC_0-24 for efficacy and safety monitoring.

Keywords: area under curve (AUC); drug monitoring; pediatrics; pharmacokinetics; vancomycin.