Abstract
Introduction
Estimation of vancomycin area under the curve (AUC) is challenging in the case of discontinuous administration. Machine learning approaches are increasingly used and can be an alternative to population pharmacokinetic (POPPK) approaches for AUC estimation.
The objectives were to train XGBoost algorithms based on simulations performed in a previous POPPK study to predict vancomycin AUC from early concentrations and a few features (i.e. patient information) and to evaluate them in a real-life external dataset in comparison to POPPK.
Patients and Methods
Six thousand simulations performed from 6 different POPPK models were split into training and test sets. XGBoost algorithms were trained to predict trapezoidal rule AUC a priori or based on 2, 4 or 6 samples and were evaluated by resampling in the training set and validated in the test set. Finally, the 2-sample algorithm was externally evaluated on 28 real patients and compared to a state-of-the-art POPPK model-based averaging approach.
Results
The trained algorithms showed excellent performances in the test set with relative mean prediction error (MPE)/ imprecision (RMSE) of the reference AUC = 3.3/18.9, 2.8/17.4, 1.3/13.7% for the 2, 4 and 6 samples algorithms respectively. Validation in real patient showed flexibility in sampling time post-treatment initiation and excellent performances MPE/RMSE<1.5/12% for the 2 samples algorithm in comparison to different POPPK approaches.
Conclusions
The Xgboost algorithm trained from simulation and evaluated in real patients allow accurate and precise prediction of vancomycin AUC. It can be used in combination with POPPK models to increase the confidence in AUC estimation.
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Acknowledgements and Disclosures
The authors thank the patients whose data were used in this study. The authors have no conflicts of interest to declare for this work.
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No funding was received for this study.
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MB, JBW, designed the work, MB, JBW, ES, ML, PM, DWU, SGW analysis and interpret the data, MB, JBW, DWU, SGW wrote the draft.
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Bououda, M., Uster, D.W., Sidorov, E. et al. A Machine Learning Approach to Predict Interdose Vancomycin Exposure. Pharm Res 39, 721–731 (2022). https://doi.org/10.1007/s11095-022-03252-8
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DOI: https://doi.org/10.1007/s11095-022-03252-8