Correlation of the vancomycin 24-h area under the concentration-time curve (AUC 24 ) and trough serum concentration in children with severe infection: A clinical pharmacokinetic study.

Background: Vancomycin is a common drug used in children with severe infection. In adults, at least 15 mg/L of the optimal vancomycin trough concentration (C _trough ) is needed to generate the target 24-h area under the concentration-time curve (AUC ₂₄ ) to the minimum inhibitory concentration (MIC) of 400 for a pathogen with the MIC ≤1 mg/L.
Objectives: To determine vancomycin PK in children with severe infection and to explore the correlation between vancomycin C _trough and AUC ₂₄ in children, as well as to propose the appropriate vancomycin dosages using Monte Carlo simulation.
Materials and Methods: Children aged 2-18 years who were admitted to Chiang Mai University Hospital and received intravenous vancomycin for severe infection were included in the study. Serum samples for vancomycin PK were obtained before and serially after the administration of the first dose according to the protocol. Pharmacokinetic analyses were performed using Phoenix WinNonlin® 7.0 and NLME™7.0.
Results: Fourteen children with 64% males and age range from 2 to 13 years were included in this study. Non-compartmental analysis revealed the median volume of distribution, clearance, and elimination half-life of 0.58 L/kg, 2.82 mL/kg/min and 2.33 h, respectively. Vancomycin serum concentrations were best described by a two-compartmental model with first-order elimination.The observed C _trough at 6 h correlated well with the AUC ₂₄ . The median vancomycin C _trough at steady state that correlated with the AUC ₂₄ ≥ 400 and <800 were 11.18, 9.50, 7.91 and 6.55 mg/L in simulated children receiving vancomycin 40, 60, 80 and 100 mg/kg/day, respectively.
Conclusion: Correlation between vancomycin C _trough and AUC ₂₄ values in children has been observed. However, the values of C _trough that correlate with the target AUC ₂₄ ≥400 in children are lower than the values observed and targeted in adults.
(Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)