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Decreased vancomycin clearance in patients with congestive heart failure

  • Pharmacokinetics and Disposition
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

Congestive heart failure (CHF) alters the pharmacokinetics of various drugs, including cardiovascular agents, due to decreased cardiac output and decreased renal blood flow. The purpose of this study was to evaluate the influence of CHF on the clearance of vancomycin, a glycopeptide antibacterial agent.

Methods

After reviewing more than 1,500 clinical charts of patients who received vancomycin therapy and whose serum vancomycin level was monitored, we identified 101 patients who also had the left ventricular ejection fraction (LVEF) assessed at that time. The fluorescence polarization immunoassay method was used to measure vancomycin serum concentrations in these patients 1 h after the end of vancomycin infusion and just before the next administration. Using these two measurements, we calculated the pharmacokinetic parameters using the Bayesian estimator.

Results

Patients with an LVEF of <40 % (16 patients) or those with an LVEF of ≥ 40 %  and <60 % (40 % ≤ LVEF < 60 % ; 32 patients) had a significantly lower vancomycin clearance than patients with LVEF of ≥60 % (53 patients) (2.29 ± 0.95 or 2.79 ± 0.99 vs. 3.50 ± 1.04 L/h; p < 0.001 or p < 0.01, respectively). Vancomycin clearance was strongly correlated not only with estimated creatinine clearance (CLcr) in patients with an LVEF of <40 % (r = 0.828) and 40 % ≤ LVEF < 60 % (r = 0.773), but also with an LVEF in patients with a CLcr of <60 mL/min (r = 0.646). Consistent with these findings, multiple regression analysis revealed that CLcr, LVEF and body weight were important independent variables for vancomycin clearance (r 2 = 0.649).

Conclusions

Vancomycin clearance decreased with decreasing cardiac function (LVEF) and decreasing CLcr. This finding suggests that vancomycin clearance is affected by cardiac function and would be predicted not only CLcr but also by LVEF.

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Acknowledgments

We thank Dr. Tomohiro Taniguchi for his valuable comments.

Conflict of interest

None.

Author information

Author notes

  1. Yuko Shimamoto

    Present address: Department of Pharmacy, National Cerebral and Cardiovascular Center, 5-7-1 Fujishiro-dai, Suita, Osaka, 565-8565, Japan

Authors and Affiliations

  1. Department of Pharmacy, National Hospital Organization–Osaka National Hospital, Osaka, Japan

    Yuko Shimamoto & Katsuya Komori

  2. Division of Clinical Pharmacology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    Tsuyoshi Fukuda & Min Dong

  3. Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA

    Tsuyoshi Fukuda

  4. Department of Infectious Diseases, National Hospital Organization–Osaka National Hospital, Osaka, Japan

    Shinjiro Tominari & Takuma Shirasaka

  5. Department of Clinical Pharmacokinetics, Niigata University of Pharmacy and Applied Life Sciences, Niigata, Japan

    Kyoko Fukumoto & Kazuyuki Ueno

  6. Department of Clinical Pharmacy and Clinical Pharmacokinetics, Osaka University of Pharmaceutical Sciences, Osaka, Japan

    Kazuhiko Tanaka

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  1. Yuko Shimamoto
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Corresponding author

Correspondence to Yuko Shimamoto.

Appendix

Appendix

Fig. 3
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Relationship between LVEF and CLcr

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Fig. 4
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Relationship between vancomycin clearance and LVEF

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Fig. 5
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Relationship between vancomycin clearance and CLcr

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Shimamoto, Y., Fukuda, T., Tominari, S. et al. Decreased vancomycin clearance in patients with congestive heart failure. Eur J Clin Pharmacol 69, 449–457 (2013). https://doi.org/10.1007/s00228-012-1340-4

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  • DOI: https://doi.org/10.1007/s00228-012-1340-4

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