Prediction of Vancomycin Area Under the Curve With Trough Concentrations Only: Performance Evaluation of Pediatric Population Pharmacokinetic Models.

backgroundIn pediatric patients, vancomycin plays a pivotal role in combating infections, necessitating precise therapeutic drug monitoring to ensure efficacy and safety. The adoption of model-informed precision dosing (MIPD) has demonstrated potential in optimizing dosing strategies based on the 24-hour area under the concentration-time curve (AUC24h). However, the predictive performance of population pharmacokinetic models by using only trough concentrations to estimate AUC24h has not been evaluated.

methodsThe predictive performance of 23 vancomycin population pharmacokinetic models was retrospectively evaluated in 2 cohorts: cohort A, 21 patients with postnatal age <50 days; cohort B, 124 patients with postnatal age ≥50 days. Multiple scenarios were investigated by using peak and trough concentration, peak concentration solely, trough concentration solely, or covariate information (a priori). The median AUC24h per patient across all models was used as the true AUC24h.

resultsFor both cohorts, the relative root mean square error (rRMSE) for the AUC24h precision based on trough concentrations was similar to the rRMSE based on a peak and trough sample. For cohort A, the models by Chen, Colin, and Mehrotra showed the best trough-based performance with the lowest relative bias (range, -3.3% to -2.6%) and rRMSE (range, 6.8%-7.3%). For cohort B, the models from Alsultan and Lv illustrated the lowest relative bias (range, 1.75% to -5.4%) and rRMSE (range, 16.6%-15.1%).

conclusionsThis study illustrates that trough concentration-based AUC24h estimation is a feasible approach in vancomycin MIPD. These findings endorse the selected models for advanced MIPD vancomycin therapy in pediatrics, although further investigation into clinical outcomes is recommended.