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Vancomycin Pharmacokinetics in Patients with Advanced Cancer Near End of Life

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

Abstract

Background and Objective

The effect of cancer cachexia on the pharmacokinetics of vancomycin remains unclear. We investigated whether the pharmacokinetics of vancomycin and the risk of kidney injury are altered with the development of cancer cachexia.

Methods

A retrospective analysis was conducted using therapeutic drug monitoring data obtained from 86 cancer patients who received vancomycin intravenously for infection. The patients were classified into four groups according to the stage of cachexia defined by international consensus—non-cachexia (n = 26), pre-cachexia (n = 10), cachexia (n = 21) and refractory cachexia (n = 29). Vancomycin pharmacokinetics were analyzed by a traditional one-compartment model and Bayesian method using plasma concentrations measured in these patients. Renal function and pharmacokinetic parameters were compared between the non-cachexia patients (n = 26) and total cancer cachexia patients (n = 60).

Result

No significant difference in estimated glomerular filtration rate was observed between the non-cachexia and the total cancer cachexia patients. In contrast, systemic clearance of vancomycin was significantly lower in the total cancer cachexia patients compared with the non-cachexia patients when analyzed by the traditional one-compartment model [median (range)—49.7 (9.8‒98.7) vs 70.2 (12.5‒211.8) mL/min, p < 0.01] and by the Bayesian method [45.6 (12.5–84.7) vs 63.3 (12.2–102.5) mL/min, p < 0.05]. None of the non-cachexia patients developed kidney injury, whereas 15% (9 of 60 patients) of the total cancer cachexia patients developed kidney injuries (p = 0.052).

Conclusions

The present study revealed that cancer patients with cachexia may have reduced vancomycin clearance compared with those without cachexia. Cancer cachexia may be a risk factor of vancomycin-associated kidney injury, independent of renal function.

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Authors and Affiliations

  1. Department of Pharmacy, NTT Medical Center Tokyo, 5-9-22 Higashi-gotanda, Shinagawa-ku, Tokyo, 141-8625, Japan

    Hirokazu Nakayama & Toshiaki Kato

  2. Department of Palliative Care, NTT Medical Center Tokyo, 5-9-22 Higashi-gotanda, Shinagawa-ku, Tokyo, 141-8625, Japan

    Masahiro Suzuki

  3. Department of Pharmacotherapy, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo, 204-8588, Japan

    Hirotoshi Echizen

Authors
  1. Hirokazu Nakayama
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  2. Masahiro Suzuki
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  3. Toshiaki Kato
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  4. Hirotoshi Echizen
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Corresponding author

Correspondence to Hirokazu Nakayama.

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Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Conflict of interest

The authors declare no conflicts of interest.

Ethics approval

The protocol of the present study was approved by Ethics Committee of NTT Medical Center Tokyo prior to the study (the approval number: 17‒227).

Informed consent

The IRB waived the requirement of written informed consent from patients, because the present study had a retrospective design and the data used were obtained from routine medical care including TDM. Nevertheless, the study was conducted with full consideration of protecting patients’ personal information according to the guidelines on privacy policy.

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Nakayama, H., Suzuki, M., Kato, T. et al. Vancomycin Pharmacokinetics in Patients with Advanced Cancer Near End of Life. Eur J Drug Metab Pharmacokinet 44, 837–843 (2019). https://doi.org/10.1007/s13318-019-00564-w

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