Vancomycin monitoring in children using bayesian estimation.
BACKGROUND
Optimal monitoring of vancomycin in children needs evaluation using the exposure target with area under the curve (AUC) of the serum concentrations versus time over 24 hours. Our study objectives were to: (1) compare the accuracy and precision of vancomycin AUC estimations using 2 sampling strategies-1 serum concentration sample (1S, near trough) versus 2 samples (2S, near peak and trough) against the rich sample (RS) method; and (2) determine the performance of these strategies in predicting future AUC against an internal validation sample (VS).


METHODS
This was a retrospective cohort study using population-based pharmacokinetic modeling with Bayesian post hoc individual estimations in nonlinear mixed effects modeling (version 7.2). Pediatric subjects 3 months-21 years of age who received vancomycin ≥48 hours and had more than 3 drug samples within the first ≤96 hours of therapy were enrolled. Outcome measures were the accuracy, precision, and internal predictive performance of AUC estimations using 2 monitoring strategies (ie, 1S versus 2S) against the RS (which was derived from modeling all serum vancomycin concentrations obtained anytime during therapy) and VS (from serum concentrations obtained after 96 hours of therapy).


RESULTS
Analysis included 138 subjects with 712 vancomycin serum concentrations. Median age was 6.1 (interquartile range, 2.2-12.2) years, weight 22 (13-38) kg, and baseline serum creatinine 0.37 (0.30-0.50) mg/dL. Both accuracy and precision were improved with the 2S, compared with 1S, for AUC estimations (-2.0% versus -7.6% and 10.3% versus 12.8%, respectively) against the RS. Improved accuracy and precision were also observed for 2S when evaluated against VS in predicting future AUC.


CONCLUSIONS
Compared with 1S, the 2S sampling strategy for vancomycin monitoring improved accuracy and precision in estimating and predicting future AUC. Evaluating 2 drug concentrations in children may be prudent to ensure adequate drug exposure.
*Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla; †Miller Children's Hospital, Long Beach; and ‡Rady Children's Hospital, San Diego, CA.
Jennifer
J
Le
Becky
B
Ngu
John S
JS
Bradley
William
W
Murray
Austin
A
Nguyen
Lyn
L
Nguyen
Gale L
GL
Romanowski
Tiana
T
Vo
Edmund V
EV
Capparelli
D000293:Adolescent; D000900:Anti-Bacterial Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D019540:Area Under Curve; D001499:Bayes Theorem; D002648:Child; D002675:Child, Preschool; D016903:Drug Monitoring; D006801:Humans; D008297:Male; D008954:Models, Biological; D012189:Retrospective Studies; D014640:Vancomycin / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*
D000900:Anti-Bacterial Agents; D014640:Vancomycin