Population pharmacokinetics models of vancomycin among critically ill
obese patients: A systematic review Running head: Population
Pharmacokinetic of vancomycin word count 5179
Abstract
Background: Vancomycin is a glycopeptide antibiotic used for
gram-positive infections. Several vancomycin population pharmacokinetic
models have been introduced in the last decades. Thus, a systematic
review was performed to compare published pharmacokinetics models and
(ii) to summarise and explore identified covariates influencing the
vancomycin pharmacokinetics models. Methods: A search of publications
for population pharmacokinetic analyses of vancomycin in critically ill
obese patients from inception to October 2022 was conducted in PubMed
and SCOPUS databases. Reviews, methodology articles, in vitro and animal
studies, and noncompartmental analyses were excluded. Data on study
characteristics, patient demographics, clinical parameters,
pharmacokinetic parameters, and outcomes were collected. Results: Six
studies were included in this review. Vancomycin pharmacokinetics was
described as one-compartment in most of the studies. Significant
interindividual variations of vancomycin pharmacokinetic parameters were
found in most of the included studies. Age, sex, body weight,
fibrinogen, aspartate aminotransferase, blood urea nitrogen, cystatin,
and concomitant nephrotoxic drugs were the most commonly identified
covariates affecting these parameters. External validation was only
performed in one study to determine the predictive performance of the
models. Conclusions. Large pharmacokinetic variability remains despite
the inclusion of several covariates. This can be improved by including
other potential factors, such as metabolic factors and significant
drug-drug interactions in a well-designed population pharmacokinetic
model in the future, taking into account the incorporation of a larger
sample size and a more stringent sampling strategy. External validation
should also be performed to the previously published models to compare
their predictive performances.