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A Population Pharmacokinetics Model for Vancomycin Dosage Optimization Based on Serum Cystatin C

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European Journal of Drug Metabolism and Pharmacokinetics Aims and scope Submit manuscript

Abstract

Background and Objectives

Renal function has an important influence on the pharmacokinetics of vancomycin, and serum cystatin C (CysC) exhibits accurate predictive performance as a marker for renal function. This study aimed to develop a population pharmacokinetics (PopPK) model of vancomycin based on serum CysC in pediatric patients. In addition, vancomycin dosage was optimized with the area under the serum concentration–time curve over 24 h (AUC0–24)/minimum inhibitory concentration (MIC) ratio in the target range of 400–700 and the steady-state trough concentration (Css,trough).

Methods

Data were retrospectively obtained from pediatric patients aged 2–18 years who received vancomycin treatment for infection from January 2014 to June 2019. PopPK analysis and Monte Carlo simulations were conducted using nonlinear mixed effects model (NONMEM) software.

Results

A total of 220 children were included. Serum CysC and age were significant covariates affecting the pharmacokinetics of vancomycin. The final typical value of clearance was 2.25 L/h; the volume of distribution was 8.17 L. The average probability of target attainment values of AUC0–24/MIC ratios within 400–700 in the 2–7, 7–12, and 12–18 years age groups were 66.1%, 68.1% and 66.5%, respectively. The median Css,trough values of vancomycin for the 2–7, 7–12, and 12–18 years age groups were 7.49–11.84, 5.98–11.32, and 5.15–11.39 mg/L, respectively, and were highly correlated with AUC0–24/MIC ratios in the range of 400–700 when the MIC was 1 mg/L.

Conclusions

The pharmacokinetic parameters for vancomycin in pediatric patients were estimated using a serum CysC model. The simulated dosages provide a reference for vancomycin therapy.

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Authors and Affiliations

  1. Department of Pharmacy, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning, 530021, Guangxi, People’s Republic of China

    Jie-Jiu Lu, Ming Chen, Chun-Le Lv, Ren Zhang, Hua Lu, Dao-Hai Cheng, Shuang-Yi Tang & Tao-Tao Liu

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  1. Jie-Jiu Lu
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  2. Ming Chen
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  3. Chun-Le Lv
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  4. Ren Zhang
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  5. Hua Lu
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  8. Tao-Tao Liu
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Correspondence to Tao-Tao Liu.

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Conflict of interest

The author reports no conflicts of interest in this work.

Ethical approval

The study protocol was approved by the Ethics Committee of the First Affiliated Hospital of Guangxi Medical University (No. 2017-KY-019).

Funding

This work was supported by the National Natural Science Foundation of China (Grant no. 81760671).

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Lu, JJ., Chen, M., Lv, CL. et al. A Population Pharmacokinetics Model for Vancomycin Dosage Optimization Based on Serum Cystatin C. Eur J Drug Metab Pharmacokinet 45, 535–546 (2020). https://doi.org/10.1007/s13318-020-00621-9

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