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Published on: February 21, 2020
A population pharmacokinetic model of vancomycin for dose individualization based on serum cystatin C as a marker of
Tao-Tao Liu1, Hui-Mei Pang1, Li Jing1
1Department of Pharmacy, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
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 (Css ) 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 Css 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.
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