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

Liu, Taotao; Pang, Hui-Mei; Li, Jing; Wei, Wenxing; Qin, Xiaoxia; Guo, Qing; Liu, Hua; Cheng, Dao-Hai; Jiang, Weizhe

doi:10.1111/jphp.13071

Cited by 13 publications

(23 citation statements)

References 47 publications

(114 reference statements)

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“…Patients with a CLcr >180 mL/min do not need to increase the dose, which is consistent with the saturation correlation dimension of our model. Other studies reported higher daily doses than ours [9,12,30]. Differences in the choice of simulation target might be the reason.…”

Section: Discussioncontrasting

confidence: 49%

“…Establishing a population pharmacokinetic model is optimal for planning dosing regimen. However, most of the studies provided only regimens for patients with impaired renal function [9][10][11][12]. The pharmacokinetic profile of vancomycin in patients with ARC has not been well established and an appropriate dosing recommendation is very necessary.…”

Section: Introductionmentioning

confidence: 99%

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Population Pharmacokinetic Modeling and Dose Optimization of Vancomycin in Chinese Patients with Augmented Renal Clearance

Zhao

Zhang

et al. 2021

Antibiotics

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Patients with augmented renal clearance (ARC) have been described as having low vancomycin concentration. However, the pharmacokinetic model that best describes vancomycin in patients with ARC has not been clarified. The purpose of this study is to determine the pharmacokinetic of vancomycin in Chinese adults and the recommend dosage for patients with different renal function, including patients with ARC. We retrospectively collected 424 vancomycin serum concentrations from 209 Chinese patients and performed a population pharmacokinetic model using NONMEM 7.4.4. The final model indicated that the clearance rate of vancomycin increased together with the creatinine clearance, and exhibited a nearly saturated curve at higher creatinine clearance. The estimated clearance of vancomycin was between 3.46 and 5.58 L/h in patients with ARC, with 5.58 being the maximum theoretical value. The central volume of distribution increased by more than three times in patients admitted to Intensive Care Unit. Monte Carlo simulations were conducted to explore the probability of reaching the target therapeutic range (24-h area under the curve: 400–650 mg·h/L, trough concentration: 10–20 mg/L) when various dose regimens were administered. The simulations indicated that dose should increase together with the creatinine clearance until 180 mL/min. These findings may contribute to improving the efficacy and safety of vancomycin in patients with ARC.

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Section: Discussioncontrasting

confidence: 49%

Section: Introductionmentioning

confidence: 99%

Population Pharmacokinetic Modeling and Dose Optimization of Vancomycin in Chinese Patients with Augmented Renal Clearance

Zhao

Zhang

et al. 2021

Antibiotics

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“…Serum cystatin C (Cys C) is a low molecular weight protein produced by all nucleated cells, and its concentration in the blood is constant and is not affected by the patient's age, body weight or sex. 5 Previous researchers have developed population pharmacokinetic models based on Cys C. [6][7][8][9] In those studies, the pharmacokinetics of vancomycin can be well predicted by the models. Other studies have also developed population pharmacokinetic models based on SCR, and the predictive performance of those models is also good.…”

Section: What Is K Nown and Objec Tivementioning

confidence: 99%

Development and comparison of population pharmacokinetic models of vancomycin in neurosurgical patients based on two different renal function markers

Liu

Guo

et al. 2019

J Clin Pharm Ther

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What is known and objectives: Some previous studies have indicated that serum cystatin C (Cys C) is a better marker than serum creatinine (SCR) for assessing the glomerular filtering rate (GFR). However, in almost all population pharmacokinetic models of vancomycin, the GFR is usually estimated from SCR. Therefore, the aim of this study was to compare the GFR estimated from SCR (sGFR) with the GFR estimated from Cys C (cGFR) and investigate which one can describe the characteristics of vancomycin population pharmacokinetics better in Chinese neurosurgical adult patients. Methods: Patients from the Neurosurgery Department aged ≥18 years were enrolled retrospectively. Among these patients, the data from 222 patients were used to establish two population pharmacokinetic models based on sGFR and cGFR, separately. The data from another 95 patients were used for the external validation of these two models. Non-linear mixed-effect modelling (NONMEM) 7.4.3 was used for the population pharmacokinetic analysis. Results: We developed two one-compartment models with first-order absorption based on Cys C and SCR, separately. In the Cys C model, age, body weight and cGFR were significant covariates on the clearance rate (CL) of vancomycin (typical value, 6.4 L/hour). In the SCR model, age and sGFR were significant covariates on the CL (typical value, 6.46 L/hour). The external validation results showed that the predictive performance of the two models was similar. What is new and conclusion: In this study, the predictive performance of two models was similar in neurosurgical patients. We did not find a significant improvement in the predictive performance of the model when GFR was estimated from Cys C.

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“…Across all 28 included studies, equations for SCr-and cysC-based estimates of kidney function varied [25]. Since 2017, additional literature has been published that corroborated these findings [37][38][39]. These studies were primarily pharmacokinetic associations or simulations.…”

Section: Medication Dosing Based On Cyscmentioning

confidence: 96%

Cystatin C: A Primer for Pharmacists

et al. 2020

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Pharmacists are at the forefront of dosing and monitoring medications eliminated by or toxic to the kidney. To evaluate the effectiveness and safety of these medications, accurate measurement of kidney function is paramount. The mainstay of kidney assessment for drug dosing and monitoring is serum creatinine (SCr)-based estimation equations. Yet, SCr has known limitations including its insensitivity to underlying changes in kidney function and the numerous non-kidney factors that are incompletely accounted for in equations to estimate glomerular filtration rate (eGFR). Serum cystatin C (cysC) is a biomarker that can serve as an adjunct or alternative to SCr to evaluate kidney function for drug dosing. Pharmacists must be educated about the strengths and limitations of cysC prior to applying it to medication management. Not all patient populations have been studied and some evaluations demonstrated large variations in the relationship between cysC and GFR. Use of eGFR equations incorporating cysC should be reserved for drug management in scenarios with demonstrated outcomes, including to improve pharmacodynamic target attainment for antibiotics or reduce drug toxicity. This article provides an overview of cysC, discusses evidence around its use in medication dosing and in special populations, and describes practical considerations for application and implementation.

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

Cited by 13 publications

References 47 publications

Population Pharmacokinetic Modeling and Dose Optimization of Vancomycin in Chinese Patients with Augmented Renal Clearance

Population Pharmacokinetic Modeling and Dose Optimization of Vancomycin in Chinese Patients with Augmented Renal Clearance

Development and comparison of population pharmacokinetic models of vancomycin in neurosurgical patients based on two different renal function markers

Cystatin C: A Primer for Pharmacists

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