A Population Pharmacokinetic Approach to Prospectively Assess Vancomycin Pharmacokinetics in Adult Jordanian Patients: a Step towards Personalized Dosing

Background: Vancomycin is a glycopeptide antibiotic that is frequently used to treat severe gram-positive bacterial infections, particularly, methicillin-resistant Staphylococcus aureus (MRSA) infections [ 1]. Being a highly variable drug with a narrow therapeutic window [ 2, 3], personalized dosing strategies are required to maximize efficacy and minimize toxicity [ 4]. Objectives: In this study, we aimed to develop a population pharmacokinetic (PopPK) model for Vancomycin utilizing data obtained from the University of Jordan Hospital, additionally to identify significant covariates that affect vancomycin disposition for implementing personalized dosing regimens. Method: Vancomycin serum concentrations were collected prospectively from patients who are 18 years or older. Demographic data such age and weight alongside relevant renal function tests were also collected. Population pharmacokinetic model was established using nlmixr2 with one-compartment model as the structural model. Pharmacokinetic parameters were analyzed for influence given the following potential covariates: weight (WT); age (AGE); estimated glomerular filtration rate (EGFR); and albumin (ALB). Model validation was performed, and the final model was used to personalize vancomycin therapy with the goal of reaching target concentrations of 10-20 μg/mL. Results: The derived model sufficiently described the pharmacokinetics of vancomycin demonstrated by a total clearance (CL) of 0.333 L/h (95% CI: 0.210-0.528) and volume of distribution (V) of 175.09 L (95% CI: 138.812-216.891). between-subject variability was for clearance (CV=12.4%) and moderate for volume of distribution (CV=33.19%). Among the investigated covariates, EGFR had a significant effect on clearance (coefficient=0.536, 95% CI: 0.097-0.975)8; neither weight effect on volume of distribution nor clearance was statistically significant. We found both a proportional (0.107) and an additive (6.046 μg/mL) component to the residual error model. Conclusion: This study showed that a population pharmacokinetic approach can accurately describe vancomycin disposition in patients at the University of Jordan Hospital, with renal function (EGFR) identified as the most important covariate of vancomycin clearance. The model developed should be useful for individualizing vancomycin dosing regimens to attain target therapeutic concentrations of 10-20 μg/mL, possibly leading to better treatment outcomes with fewer adverse effects.