Systematic external evaluation of reported population pharmacokinetic models of vancomycin in Chinese children and adolescents.

Journal of Clinical Pharmacy and Therapeutics
Chunle LvYiyu Chen

Abstract

Various population pharmacokinetic (PopPK) models for vancomycin in children and adolescents have been constructed to optimize the therapeutic regimen of vancomycin. However, little is known about their predictive performance when extrapolated to different clinical centres. Therefore, the aim of this study was to externally validate the predictability of vancomycin PopPK model when extrapolated to different clinical centres and verify its applicability in an independent data set. The published models were screened from the literature and evaluated using an external data set of a total of 451 blood concentrations of vancomycin measured in 220 Chinese paediatric patients. Prediction- and simulation-based diagnostics and Bayesian forecasting were performed to evaluate the predictive performance of the models. Ten published PopPK models were assessed. Prediction-based diagnostics showed that none of the investigated models met all the standards (median prediction error (MDPE) ≤ ±20%, median absolute prediction error (MAPE) ≤30%, PE% within ±20% (F20 ) ≥35% and PE% within ±30% (F30 ) ≥50%), indicating unsatisfactory predictability. In simulation-based diagnostics, both the visual predictive checks (VPC) and the normalized prediction...Continue Reading

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