Influences of renal function descriptors on population pharmacokinetic modeling of vancomycin in Chinese adult patients

Abstract

Vancomycin, a glycopeptide antibiotic for the treatment of grampositive infections, is mainly eliminated via glomerular filtration. Thus, its therapeutic effects are affected predominantly by renal function. The aim of this study was to develop a population pharmacokinetic model of vancomycin for Chinese adult patients and to investigate the influence of different renal function descriptors on the predictability of the model. A retrospective analysis was performed based on the blood concentrations of vancomycin in 218 Chinese adult patients. Among these patients, the data from 160 were used to establish the population pharmacokinetic model, and the data from the remaining 58 patients were used for external model validation. A simulation was employed to determine the appropriate initial vancomycin dosage regimens in adult Chinese patients for reaching the target steady-state trough concentrations of 10-15 mg/L and 15-20 mg/L. We developed a one-compartment model with first-order absorption to characterize the concentration-time profile of vancomycin. There was a positive correlation between the body clearance of vancomycin and renal function; both creatinine clearance (CL) and age were the covariates that influenced the PK of vancomycin, and the excretion of vancomycin decreased as renal function diminishing with age. The typical clearance (CL) value was 2.829 L/h for 75-year-old patients with CL values of 80 mL/min, and the rate constant of CL with the CL changing at 1 mL/min was 0.00842. The influence coefficient of age on CL was 0.08143. The external validation results revealed that the current different descriptors of renal function behaved similarly to the predicted performance of the models. In conclusion, the developed model is appropriate for Bayesian dose predictions of vancomycin concentrations in the population of Chinese adult patients. Furthermore, the simulation provides a reference for clinical optimized antibacterial therapy with vancomycin.

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

“…An appropriate PPK model is of importance for achieving vancomycin targeted C ss . Traditionally, vancomycin dosage was determined based on the CLcr estimated by Scr, and most of the vancomycin PPK models were focused on the CLcr . However, many other studies had shown that cystatin C predicted vancomycin trough levels better than Scr in hospitalized patients, and a vancomycin dosing nomogram based on GFR estimated by cystatin C could improve goal trough achievement compared to Scr .…”

“…The guideline of therapeutic drug monitoring for vancomycin recommends that vancomycin dosage should be administered and adjusted individually based on PPK models . PPK models of vancomycin were very common, but most of them incorporated the CLcr as the renal function covariate, which are considered to be defective in estimating renal function. There were only a few PPK models developed optimal dosing regimens according to different CLcr levels .…”

“…PPK models of vancomycin were very common, but most of them incorporated the CLcr as the renal function covariate, which are considered to be defective in estimating renal function. There were only a few PPK models developed optimal dosing regimens according to different CLcr levels . Although there were two PPK models established with cystatin C as renal biomarker, the populations and modelling processes between these two studies differed greatly, and both of them failed to develop optimal dosing regimens based on GFR levels with cystatin C as estimated marker.…”

The effect of the body mass index and creatinine clearance on serum trough concentration of vancomycin in adult patients

“…The clinical guidelines recommend always keeping trough vancomycin concentrations above 10 μg/mL, and a trough vancomycin concentration of 15-20 μg/mL is recommended in more serious infections [3]. As the elimination of vancomycin relies almost exclusively on glomerular filtration, renal function is one of the most important factors influencing patient exposure to vancomycin [4].…”

Pharmacokinetics of vancomycin in patients with different renal function levels

“…Interestingly, patients with hemorrhagic stroke had higher values of vancomycin clearance [ 7 ]. Renal function was identified as an important determinant of vancomycin clearance in several other studies, but only in some studies it was observed that declining creatinine clearance with old age contributed to decreased vancomycin clearance [ 8 ]. However, determinants of vancomycin clearance were not analyzed separately in populations with different levels of renal function, which could be why some important factors could have been missed.…”