Review and Validation of Bayesian Dose‐Optimizing Software and Equations for Calculation of the Vancomycin Area Under the Curve in Critically Ill Patients

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Abstract
Background Vancomycin area under the time‐concentration curve (AUC) has been linked to efficacy and safety. An accurate method of calculating the AUC is needed. Methods Bayesian dose optimizing software programs available for clinician use and first‐order pharmacokinetic equations were evaluated for their ability to estimate vancomycin AUC. A previously published rich pharmacokinetic dataset of 19 critically‐ill patients was used for validation of the AUC estimation. The AUC estimated using subsets of the full dataset by Bayesian software and equations was compared with the reference AUC. Accuracy (ratio of estimated AUC to the reference AUC) and bias (percent difference of estimated AUC to reference AUC) were calculated. Results Five Bayesian dose optimizing software programs (APK©, Best DoseTM, DoseMe®, Insight‐Rx©, and PrecisePKTM) and 2 first‐order pharmacokinetic equations were included. Of the Bayesian programs, Insight‐Rx was the most adaptable, visually appealing, easiest to use, and had the most company support. Utilizing only the trough, accuracy (range from 0.79 to 1.03) and bias (range from 5.1% to 21.2%) of the Bayesian dose optimizing software were variable. PrecisePK and Best Dose had the most accurate estimates with the accuracy values of Best Dose exhibiting the most variability of all the programs; however, both programs were more difficult to use. PrecisePK was the least biased (median of 5.1%). Using a single, non‐trough value produced similar results to that of the trough for most programs. The addition of a second level to the trough improved the accuracy and bias for DoseMe and Insight‐Rx but not PrecisePK and Best Dose. APK did not reliably estimate the AUC with input of 2 levels. Using 2 levels, the pharmacokinetic equations produced similar or better accuracy and bias as compared with Bayesian software. Conclusion Bayesian dose optimizing software using 1 or more vancomycin levels and pharmacokinetic equations utilizing 2 vancomycin levels produce similar estimates of the AUC.

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