Factors Affecting Vancomycin Trough Concentration; a Population Pharmacokinetic Model in Non-Critical Care Saudi Patients.

Abstract

Background and objective: Vancomycin is commonly prescribed in treatment of methicillin-resistant Staphylococcus aureus infections. While, vancomycins' pharmacokinetic vary among older patients, there is a paucity of data regarding specific characteristics influencing pharmacokinetics in Saudi adult patients. This study aims to establish a population-pharmacokinetic (Pop-PK) model for vancomycin in patients admitted to medical wards, with the focus on identification of patient characteristics influencing vancomycin trough concentrations.

Methods: A multicenter retrospective study was conducted involving patients aged ≥40 years admitted to medical wards in the Eastern Province, Saudi Arabia and initiated on vancomycin, between January to December 2022. Non-linear mixed-effects modelling (Monolix) was employed to develop the Pop-PK model. A base model was selected based on the Akaike information criterion. Covariates considered included age, sex, body weight, C-reactive protein (CRP), serum creatinine, creatinine clearance (CrCl), and albumin levels. A P-value of <0.05 was considered statistically significant for inclusion of covariates in the final model by stepwise addition. The simulation performance of the model was assessed by visual predictive check plot. The final model was simulated using Simulx software to assess the effect of the included covariates on vancomycin trough concentration.

Results: A total of 172 vancomycin trough concentrations from 124 patients were analyzed. The final Pop-PK model characterized vancomycin trough concentrations was one compartment distribution with linear elimination. CrCl and CRP were the only covariates included in the final model, as they reduced the between-subject variability (BSV) for clearance (from 173% to 81%). The simulated model demonstrated that high CRP value and low CrCl contributed to increased vancomycin trough concentrations.

Conclusion: This study highlights large BSV in trough concentrations among patients and emphasizes the influencing of CrCl and CRP on vancomycin pharmacokinetics in medical care settings.