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Comparative polymyxin B pharmacokinetics in critically ill patients with renal insufficiency and in continuous veno-venous hemodialysis

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Abstract

Purpose

The aim of this study was to assess polymyxin B pharmacokinetics (PK) in patients with varying degrees of renal dysfunction and in patients who require continuous veno-venous hemodialysis (CVVHD).

Methods

The study enrolled 37 patients with sepsis, including 13 patients with glomerular filtration rate (GFR) below 80 mL/min and 11 patients on CVVHD. Each patient received a loading dose of polymyxin B (200–300 mg) and at least 3 subsequent doses of 100–150 mg every 12 h. For every patient, 6–8 blood samples were collected between doses. Polymyxin B (PMB) serum concentration was determined using enzyme-linked immunosorbent assay.

Results

In sepsis, patients with preserved renal function mean area under the curve over 24 h (AUC0–24 h) value reached 67.8 ± 9.8 mg*h/L, while in patients with GFR below 80 mL/min, mean AUC0–24 h was 87 ± 5.8 mg*h/L. PMB PK in patients with renal insufficiency was characterized by significantly lower clearance (CL) compared to the normal renal function group (2.1 ± 0.1 L/h vs 3.9 ± 0.4 L/h respectively). In patients on CVVHD, mean AUC0–24 h was 110.4 ± 10.3 mg*h/L, while CL reached 2 ± 0.23 L/h. The median recovery rate from dialysate constituted 22%. Simulation of different dosage regimens that indicate a fixed maintenance dose of 100 mg q12h with a loading dose of 200 mg is optimal for patients on CVVHD, and no dosage increase is required.

Conclusion

This study demonstrates decreased clearance of PMB in patients with renal insufficiency, which puts them at risk of toxicity. Therefore, patients with extremes of renal function might benefit from therapeutic drug monitoring. For patients with anuria, who require CVVHD, we suggest a fixed dose of 100 mg q12h.

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Availability of data and material

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgements

The authors acknowledge the personnel of Clinical Hospital #1 MEDSI intensive care unit for their help with sample and data collection.

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Authors and Affiliations

  1. I.I. Mechnikov Research Institute for Vaccines and Sera, Moscow, 105064, Russia

    Yury A. Surovoy, Maksim A. Burkin & Inna A. Galvidis

  2. Faculty of Medicine, M.V. Lomonosov Moscow State University, Moscow, 119991, Russia

    Yury A. Surovoy, Onur Can Rende & Sergei V. Tsarenko

  3. Moscow City Clinical Hospital #52, Moscow, 123182, Russia

    Mikhail A. Sobolev & Sergei V. Tsarenko

Authors
  1. Yury A. Surovoy
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  2. Maksim A. Burkin
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  3. Inna A. Galvidis
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  4. Mikhail A. Sobolev
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  5. Onur Can Rende
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  6. Sergei V. Tsarenko
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Contributions

YAS: writing—original draft preparation, PK, and statistical analysis. MAB: conceptualization, formal analysis and investigation, review, and editing. IAG: methodology, formal analysis, and validation. MAS: sample collection, PK, and statistical analysis. OCR: sample collection, PK, and statistical analysis. SVT: supervision, writing—review and editing. All authors have read and agreed to the published version of the manuscript.

Corresponding author

Correspondence to Yury A. Surovoy.

Ethics declarations

Ethical approval

The research was conducted in accordance with the Declaration of Helsinki and national and institutional standards. This study was approved by MEDSI Clinic Independent Ethical Committee, Moscow, Russia (Protocol #29 April 15, 2021).

Consent to participate

Informed consent form was signed by legal representatives of the patients.

Consent for publication

Informed consent form was signed by legal representatives of the patients.

Competing interests

The authors declare no competing interests.

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Keypoints

• Acute kidney injury has significant impact on polymyxin B clearance, and therapeutic drug monitoring might be beneficial in certain groups of critically ill patients.

• Continuous veno-venous hemodialysis does not lead to significant removal of polymyxin B; therefore, a fixed dosage regimen of 100 mg twice daily might be appropriate in these patients.

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Surovoy, Y.A., Burkin, M.A., Galvidis, I.A. et al. Comparative polymyxin B pharmacokinetics in critically ill patients with renal insufficiency and in continuous veno-venous hemodialysis. Eur J Clin Pharmacol 79, 79–87 (2023). https://doi.org/10.1007/s00228-022-03415-x

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