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Introduction <p>Vancomycin is a glycopeptide antibiotic commonly prescribed to treat severe gram-positive infections; however, it has a narrow therapeutic range and potentially induces nephrotoxicity following overdosing. Most studies have revealed that renal function is the main factor influencing vancomycin clearance. However, the effects of cardiac insufficiency, which usually occurs early following surgery and can cause changes in the pharmacokinetics of various drugs, likely due to decreased cardiac output, on vancomycin metabolism are poorly understood.</p> Aim <p>This study aimed to establish a vancomycin population pharmacokinetic model in patients undergoing cardiac surgery and simultaneously explore the effects of renal and cardiac functions on vancomycin pharmacokinetics.</p> Method <p>Three hundred twenty patients treated with vancomycin were enrolled. The patients’ vancomycin treatment history, specific vancomycin administration and sampling times, and laboratory test results were obtained from the electronic medical records. The data were analyzed using nonlinear mixed effects modeling. Model accuracy and robustness were evaluated with a goodness-of-fit plot, bootstrap resampling, and visual predictive checks. The vancomycin dosage strategy was simulated with a virtual patient using the pharmacokinetic parameters of the established model in different clinical scenarios.</p> Results <p>A one-compartment model was used to determine vancomycin pharmacokinetics. The estimated clearance (CL) and distribution volume (V) of vancomycin were 3.22 L/h and 88.3 L, respectively. The interindividual variabilities in CL and V were 26.0% and 48.9%, respectively, while the corresponding interoccasion variabilities were 8.9% and 13.6%. CL decreased as serum creatinine (Scr), cystatin C (CysC) and N-terminal pro-B-type natriuretic peptide levels increased. V decreased as the CysC levels and neutrophil counts increased but increased with age. The highest percentage of the within 24-h target area under the concentration curve (400–650&#xa0;mg*h/L) for the virtual patient across the different clinical scenarios was 52.4–65.2%.</p> Conclusion <p>A vancomycin population pharmacokinetic model was established for cardiac surgery patients. Both renal and cardiac functions have confirmed effects on vancomycin pharmacokinetics.</p>

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Exploring the effects of renal and cardiac functions on the pharmacokinetics of vancomycin in patients undergoing cardiac surgery: a population pharmacokinetic analysis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月21日

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  • Yinglong Ding,
  • Ling Xue,
  • Qiong Qin,
  • Haoyue Huang,
  • Yihuan Chen,
  • Han Shen,
  • Yanqiu Hu,
  • Yupeng Chen,
  • Liyan Miao,
  • Zhenya Shen

摘要

Introduction

Vancomycin is a glycopeptide antibiotic commonly prescribed to treat severe gram-positive infections; however, it has a narrow therapeutic range and potentially induces nephrotoxicity following overdosing. Most studies have revealed that renal function is the main factor influencing vancomycin clearance. However, the effects of cardiac insufficiency, which usually occurs early following surgery and can cause changes in the pharmacokinetics of various drugs, likely due to decreased cardiac output, on vancomycin metabolism are poorly understood.

Aim

This study aimed to establish a vancomycin population pharmacokinetic model in patients undergoing cardiac surgery and simultaneously explore the effects of renal and cardiac functions on vancomycin pharmacokinetics.

Method

Three hundred twenty patients treated with vancomycin were enrolled. The patients’ vancomycin treatment history, specific vancomycin administration and sampling times, and laboratory test results were obtained from the electronic medical records. The data were analyzed using nonlinear mixed effects modeling. Model accuracy and robustness were evaluated with a goodness-of-fit plot, bootstrap resampling, and visual predictive checks. The vancomycin dosage strategy was simulated with a virtual patient using the pharmacokinetic parameters of the established model in different clinical scenarios.

Results

A one-compartment model was used to determine vancomycin pharmacokinetics. The estimated clearance (CL) and distribution volume (V) of vancomycin were 3.22 L/h and 88.3 L, respectively. The interindividual variabilities in CL and V were 26.0% and 48.9%, respectively, while the corresponding interoccasion variabilities were 8.9% and 13.6%. CL decreased as serum creatinine (Scr), cystatin C (CysC) and N-terminal pro-B-type natriuretic peptide levels increased. V decreased as the CysC levels and neutrophil counts increased but increased with age. The highest percentage of the within 24-h target area under the concentration curve (400–650 mg*h/L) for the virtual patient across the different clinical scenarios was 52.4–65.2%.

Conclusion

A vancomycin population pharmacokinetic model was established for cardiac surgery patients. Both renal and cardiac functions have confirmed effects on vancomycin pharmacokinetics.