A Systematic Review of Pharmacokinetic Models of Vancomycin in Adult Patients (2020-2024): Trends, Variability, and Key Covariates.

introductionThis systematic review aimed to identify, evaluate, and critically an-alyze pharmacokinetic models of vancomycin in adult populations published in PubMed and EMBASE between 2020 and 2024. MATERIALS AND

methodsTwenty-two studies were included, describing 24 models character-ized by substantial heterogeneity in terms of study populations, methodological design, and covariate selection. Most models were developed in Asia and focused on hospitalized patients, particularly those in intensive care units (ICUs). Data from 2150 patients were analyzed, with an average of 93 patients per model.

resultsThe models demonstrated high variability in pharmacokinetic parameters, such as vancomycin clearance (Cl) and volume of distribution (Vd), influenced by factors, such as renal function, weight, age, and comorbidities. The meta-analysis conducted on clearance and interindividual variability in clearance (IIV Cl) revealed high heterogeneity among the ana-lyzed studies. The average vancomycin clearance was 4.23 L/h, with higher values observed in neurosurgical, oncohematologic patients, and those with increased renal function. The vol-ume of distribution showed greater variability in obese patients and those undergoing continu-ous renal replacement therapy. Creatinine clearance (ClCr) was identified as a significant co-variate in 66% of the models, while weight was significant in 33%. Other important covariates included age, sex, serum creatinine, serum urea, and the hospital admission unit. The meta-analysis of Cl and IIV Cl showed high heterogeneity among the studies, with I² values of 0.83 for Cl and 0.98 for IIV Cl, indicating substantial variability. DISCUSSION: The limitations of this study included the diversity of the analyzed populations, which made it challenging to assess the model's suitability. While the models showed advances in precision, challenges, such as the lack of external validation and discrepancies in dosing recommendations, remain.

conclusionThis review paper has highlighted the need to validate models in diverse popula-tions and clinical settings to optimize personalized vancomycin therapy in adults. The findings have highlighted the importance of validating or adapting pharmacokinetic models to the spe-cific characteristics of each hospital population.