Population pharmacokinetics of vancomycin in patients with liver dysfunction

Background and Objective Vancomycin is widely used in the treatment of serious infections caused by multidrug-resistant Gram-positive pathogens. However, the pharmacokinetic characteristics of vancomycin in patients with liver dysfunction remain inadequately characterized. This study aimed to develop a population pharmacokinetic (PopPK) model of vancomycin in patients with liver dysfunction and identify significant factors affecting plasma concentrations to guide individual therapy. Methods In this retrospective cohort study, clinical data were collected from patients with liver dysfunction. A nonlinear mixed effects model was employed to describe the influence of covariates on vancomycin pharmacokinetics and to obtain the final PopPK model. Goodness-of-fit plots, bootstrap analysis, and visual predictive checks were applied to assess the model stability and predictive performance. Results A total of 163 observable concentrations from 105 patients with liver dysfunction were included for PopPK modeling. A one-compartment model with first-order elimination best described the data, yielding a central volume of distribution (V) of 147.47 L and clearance (CL) of 4.40 L/h. Albumin (ALB) and estimated glomerular filtration rate (eGFR) were identified as significant covariates on V and CL in the final PopPK model, respectively. Model validation further demonstrated the excellent stability and predictive performance. Conclusion The PopPK model incorporating ALB and eGFR can be used for model-informed precision dosing in this population, potentially improving target attainment of vancomycin and reducing the risk of nephrotoxicity.