External Evaluation of Intravenous Vancomycin Population
Pharmacokinetics Models in Adults Receiving High-flux Intermittent
Hemodialysis
Abstract
Patients undergoing hemodialysis (HD) are at greater risk of
methicillin-resistant Staphylococcus aureus infections requiring
intravenous vancomycin. Close vancomycin therapeutic drug monitoring is
warranted in HD patients as renal clearance is the primary elimination
pathway. Clinically, population pharmacokinetics (popPK) model‐informed
dosing is commonly used. This study aimed to perform an external
evaluation of published vancomycin popPK models developed for adults
undergoing high-flux intermittent HD, and to create a dosing nomogram
derived from the best performing model. A literature review was
conducted through PubMed and EMBASE to identify relevant popPK models.
External dataset was collected retrospectively from patients of two
healthcare centers in Quebec, Canada. Selected models were implemented
in NONMEM (v7.5; ICON Development Solutions). Predictive performance was
assessed through prediction and simulation-based diagnostics. Results
analyses and graphical representations were then performed with
Microsoft Excel (v16.69.1; Microsoft Office), R (v4.3.1; Posit Software)
and R Studio (v1.4; Posit Software). A total of 2386 vancomycin
concentrations were collected from 274 patients and 476 antibiotic
courses. Four vancomycin popPK models were selected for evaluation. None
of the models demonstrated overall satisfactory and clinically
acceptable predictive performance. Nonetheless, Bae et al.’s model was
the best performing with a MDPE of 16.25% and MDAPE of 34.66%.
Different predictive performance was also observed for vancomycin
concentrations from samples collected during and between HD sessions.
All evaluated models presented poor overall predictive performance.
Further studies are required, through existing popPK model parameters
re-estimation or new model development, to adequately describe
vancomycin pharmacokinetics for our high-flux intermittent HD patients’
cohort.