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J Pharm Pharmacol. 2019 Jun;71(6):945-955. doi: 10.1111/jphp.13071. Epub 2019 Mar 14.

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

Author information

1
Department of Pharmacy, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
2
Department of Pharmacology, Guangxi Medical University, Nanning, Guangxi, China.

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 (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.

KEYWORDS:

cystatin C; dosing regimens; population pharmacokinetics; vancomycin

PMID:
30873627
DOI:
10.1111/jphp.13071

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