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Unbound fraction of vancomycin in intensive care unit patients

Authors

  • Martin G. Kees MD,

    Corresponding author
    1. Department of Anesthesiology and Intensive Care, Charité University Hospital Berlin - Campus Benjamin Franklin, Berlin, Germany
    2. Department of Clinical Pharmacy and Biochemistry, Institute of Pharmacy, Freie Universitaet Berlin, Berlin, Germany
    • Corresponding author:

      Martin G. Kees, Department of Anesthesiology and Intensive Care, Charité University Hospital Berlin—Campus Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin, Germany.

      E-mail: martin.kees@charite.de, martin.kees@web.de

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  • Sebastian G. Wicha,

    1. Department of Clinical Pharmacy and Biochemistry, Institute of Pharmacy, Freie Universitaet Berlin, Berlin, Germany
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  • Astrid Seefeld,

    1. Department of Pharmacology, University of Regensburg, Regensburg, Germany
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  • Frieder Kees PhD,

    1. Department of Pharmacology, University of Regensburg, Regensburg, Germany
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  • Charlotte Kloft PhD

    1. Department of Clinical Pharmacy and Biochemistry, Institute of Pharmacy, Freie Universitaet Berlin, Berlin, Germany
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  • Financial disclosure: none to declare.

Abstract

Published data on the unbound fraction of vancomycin in patient samples exhibit high variability. In the present study, a robust ultrafiltration method was developed and applied to 102 clinical samples from 22 intensive care unit patients who were treated with continuous infusion of vancomycin. A validated HPLC method was used for determination of total and unbound concentrations. The mean unbound fraction was 67.2% (standard deviation 7.5%, range 47.2–92.1%) and independent of total concentration of vancomycin or of albumin. The unbound fraction was significantly correlated (r = +0.67, P = .0009) with the renally filtered fraction (drug clearance/creatinine clearance), providing functional evidence for the validity of the measurements. Ultrafiltration proved to be susceptible to variations in the experimental conditions such as pH, temperature and centrifugal force. The measured unbound fraction increased from 60% at pH 6 to 100% at pH 9, from 57% at 4°C to 80% at 37°C, and was 76% at 1,000 g compared with 45% at 10,000 g. Lack of standardization may therefore partly explain the variable results reported in the literature.

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