A population pharmacokinetic model of vancomycin for dose individualization based on serum cystatin C as a marker of renal function

Abstract

Objectives: This study aimed to establish a vancomycin population pharmacokinetics (PPK) model based on serum cystatin C and to optimize dosing for achieving targeted steady-state trough concentrations (C ss ) of 10–15 and 15–20 mg/l. Methods: Patients aged ≥18 years were prospectively enrolled. A vancomycin PPK model was built with glomerular filtration rate (GFR) as a renal covariate estimated by cystatin C. A new group of patients were used for external evaluation. PPK analysis and Monte Carlo simulations were performed using nonlinear mixed effect modelling programme. Key findings: Two hundreds of patients with 514 samples were included. The final model was CL (L/h) = (5.07 × (GFR/105.5) 0.524 × (AGE/48.5) −0.309 × (WT/60) 0.491 ); V (l) = 46.3. Internal and external evaluations demonstrated good stability and predictability. The average probability of target attainment (PTA) of optimal dosing regimens for targeted C ss achieving 10–15 and 15–20 mg/l were 51.2% and 40.6%, respectively. An average PTA ≥71% for targeted concentration of 10–20 mg/l was obtained. Conclusions: A vancomycin PPK model with cystatin C as the renal marker has good stability and predictability. The new proposed dosing regimens were predicted to achieve a good PTA.