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Pharmacokinetics and protein binding of cefazolin in morbidly obese patients

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Abstract

Purpose

The aim of this study was to assess the pharmacokinetics and protein binding of cefazolin in morbidly obese patients undergoing bariatric surgery, to study the influence of bodyweight measures and age on pharmacokinetic parameters and to evaluate unbound cefazolin concentrations over time in this population.

Methods

Twenty morbidly obese patients (bodyweight 112–260 kg, body mass index 38–79 kg m−2) were studied following the administration of cefazolin 2 g at induction of anaesthesia. Blood samples were collected up to 4 h post-dosing to determine total and unbound plasma cefazolin concentrations. Non-compartmental pharmacokinetic data analysis was performed.

Results

Cefazolin clearance was 4.2 ± 1.0 L h−1 (mean ± standard deviation) and showed a negative correlation with age (p = 0.003) but not with bodyweight measures (p > 0.05). Volume of distribution was 13.0 ± 3.1 L and correlated positively with bodyweight measures (p ≤ 0.001). Saturable protein binding was observed with a median protein binding of 79% (interquartile range 74–82), which proved similar to reported protein binding in non-obese patients. In all patients, unbound cefazolin concentrations remained above 1 mg L−1 (minimal inhibitory concentration for 90% (MIC90) of methicillin-sensitive isolates of Staphylococcus aureus in Europe) until 4 h post-dosing.

Conclusions

Younger age—and not bodyweight—was significantly associated with higher cefazolin clearance. However, as in all patients with bodyweights up to 260 kg, unbound plasma cefazolin concentrations remained above 1 mg L−1 until 4 h after the intravenous administration of a 2-g dose. As such, re-dosing within 4 h or dosing with another antibiotic class should only be considered in the case of a higher MIC90 of the local isolates.

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Acknowledgements

The authors wish to acknowledge B. Bliemer and S. Samsom for their support in this research project.

Financial statement

This work was performed in the St. Antonius Hospital in Nieuwegein. There was no financial support or institutional departmental funding

Author information

Author notes

  1. Simone van Kralingen

    Present address: Department of Anaesthesiology, St. Lucas Andreas Hospital, Jan Tooropstraat 164, 1061 AE, Amsterdam, The Netherlands

Authors and Affiliations

  1. Department of Anaesthesiology, St. Antonius Hospital, Koekoekslaan 1, 3435 CM, Nieuwegein, The Netherlands

    Simone van Kralingen & Eric P. van Dongen

  2. Department of Clinical Pharmacy, St. Antonius Hospital, Nieuwegein, The Netherlands

    Margot Taks, Jeroen Diepstraten, Ewoudt M. van de Garde, Vera H. Deneer & Catherijne A. Knibbe

  3. Department of Surgery, St. Antonius Hospital, Nieuwegein, The Netherlands

    Marinus J. Wiezer & Bert van Ramshorst

  4. Department of Microbiology, St. Antonius Hospital, Nieuwegein, The Netherlands

    Bart Vlaminckx

  5. Division of Pharmacology Leiden/Amsterdam Center for Drug Research, Leiden University, P.O. Box 9502, 2300 RA, Leiden, The Netherlands

    Catherijne A. Knibbe

Authors
  1. Simone van Kralingen
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  2. Margot Taks
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Corresponding author

Correspondence to Simone van Kralingen.

Additional information

ClinicalTrials.gov identifier: NCT01097148 (POP-II).

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van Kralingen, S., Taks, M., Diepstraten, J. et al. Pharmacokinetics and protein binding of cefazolin in morbidly obese patients. Eur J Clin Pharmacol 67, 985–992 (2011). https://doi.org/10.1007/s00228-011-1048-x

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  • DOI: https://doi.org/10.1007/s00228-011-1048-x

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