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

摘要

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 x (GFR/105.5)(0.524) x (AGE/48.5)(-0.309) x (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.