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Therapeutic drug monitoring of once daily aminoglycoside dosing: comparison of two methods and investigation of the optimal blood sampling strategy

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

Abstract

Purpose

Therapeutic drug monitoring of patients receiving once daily aminoglycoside therapy can be performed using pharmacokinetic (PK) formulas or Bayesian calculations. While these methods produced comparable results, their performance has never been checked against full PK profiles. We performed a PK study in order to compare both methods and to determine the best time-points to estimate AUC0-24 and peak concentrations (C max).

Methods

We obtained full PK profiles in 14 patients receiving a once daily aminoglycoside therapy. PK parameters were calculated with PKSolver using non-compartmental methods. The calculated PK parameters were then compared with parameters estimated using an algorithm based on two serum concentrations (two-point method) or the software TCIWorks (Bayesian method).

Results

For tobramycin and gentamicin, AUC0-24 and C max could be reliably estimated using a first serum concentration obtained at 1 h and a second one between 8 and 10 h after start of the infusion. The two-point and the Bayesian method produced similar results. For amikacin, AUC0-24 could reliably be estimated by both methods. C max was underestimated by 10–20 % by the two-point method and by up to 30 % with a large variation by the Bayesian method.

Conclusions

The ideal time-points for therapeutic drug monitoring of once daily administered aminoglycosides are 1 h after start of a 30-min infusion for the first time-point and 8–10 h after start of the infusion for the second time-point. Duration of the infusion and accurate registration of the time-points of blood drawing are essential for obtaining precise predictions.

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Acknowledgments

The authors would like to thank Claudia Bläsi, Luisa Baselgia-Jeker, and Beatrice Vetter for the excellent technical assistance.

Conflict of interest

None of the authors reports any conflict of interest with this work.

Funding source

This study was supported by a grant from the Swiss National Science Foundation to SK (SNF 31003A-132992).

Contribution of the authors

Lana Nezic: Prepared the first protocol, helped in the practical patient work, analyzed data, and approved the final version of the manuscript

Adrian Derungs: Helped in the practical patient work, analyzed data, helped to write the manuscript, and approved its final version

Marcel Bruggisser: Helped in preparing the final version of the protocol, helped in the practical patient work, and approved the final version of the manuscript

Sarah Tschudin-Sutter: Helped in preparing the final version of the protocol as an expert in infectiology and approved the final version of the manuscript

Stephan Krähenbühl: Approved the final version of the protocol, helped in writing the manuscript, and approved its final version

Manuel Haschke: Helped in preparing the final version of the protocol, analyzed data, helped in writing the manuscript, and approved its final version

Author information

Authors and Affiliations

  1. Division of Clinical Pharmacology and Toxicology, University Hospital Basel, 4031, Basel, Switzerland

    Lana Nezic, Adrian Derungs, Marcel Bruggisser, Stephan Krähenbühl & Manuel Haschke

  2. University Clinic for Nephrology, Hypertension and Clinical Pharmacology, University Hospital Bern, Bern, Switzerland

    Adrian Derungs

  3. Department of Biomedicine, University of Basel, Basel, Switzerland

    Stephan Krähenbühl & Manuel Haschke

  4. Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Switzerland

    Sarah Tschudin-Sutter

Authors
  1. Lana Nezic
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  2. Adrian Derungs
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  3. Marcel Bruggisser
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  4. Sarah Tschudin-Sutter
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  5. Stephan Krähenbühl
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Corresponding author

Correspondence to Stephan Krähenbühl.

Additional information

Lana Nezic, Adrian Derungs, and Marcel Bruggisser contributed equally to this work.

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Supplementary Table 1

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Nezic, L., Derungs, A., Bruggisser, M. et al. Therapeutic drug monitoring of once daily aminoglycoside dosing: comparison of two methods and investigation of the optimal blood sampling strategy. Eur J Clin Pharmacol 70, 829–837 (2014). https://doi.org/10.1007/s00228-014-1680-3

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  • DOI: https://doi.org/10.1007/s00228-014-1680-3

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