Abstract
Background
Accurate dosing of vancomycin is difficult due to high inter-individual variability of vancomycin pharmacokinetics (PK), and is particularly challenging in obese patients. Vancomycin is hydrophilic, yet total body weight (TBW) has traditionally been used for dosing in the general population, and also into the obese population. The aim of this study was to evaluate the performance of published vancomycin PK models in a large set of routine clinical data obtained from an obese population.
Methods
De-identified data were available from 1717 courses of vancomycin administered to obese adults (BMI ≥ 30) from hospitals across the United States, EU, and Australia. Three population PK models, Buelga et al. (2005), Goti et al. (2018), and an obese-specific model, Adane et al. (2015), were used to predict plasma concentrations at the time of each recorded vancomycin assay, and their accuracy and bias were compared. Goodness of fit at both the population and individual level was assessed, and elastic net regression was used to identify any sources of predictive error in the obese-specific model. Model parameters for each model were then re-estimated, and a variety of body size metrics were evaluated.
Results
The Buelga et al. one-compartment model had the best predictive ability (Table 1). In all models, bias (calculated as MME; mean per-patient mean predictive error) by obesity class was observed at both the population and individual levels, and unexpectedly was largest in the obese-specific model. In the obese-specific model, predictive error correlated with the use of TBW as a model covariate. A set of models derived from Adane et al. model were then developed to correct for weight. Using ideal body weight (IBW) on Vd and no correction for weight on CL provided the best fit. The derived model accounted for 81% of variance in plasma concentration and exhibited negligible bias by obesity class (population MME = -0.75 (i), -0.06 (ii), and -0.50 (iii) mg/L; individual MME = −0.20 (i), −0.02 (ii), and −0.02 (iii) mg/L).
Conclusion
Existing vancomycin population PK models for use in the obese population are biased in higher obesity classes due to the use of total body weight. A novel population PK model developed using ideal body weight exhibits negligible bias across obesity classes as well as improved predictive ability.
Disclosures
All authors: No reported disclosures.
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