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Population pharmacokinetics of prophylactic cefoxitin in patients undergoing colorectal surgery

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

Abstract

Purpose

To elucidate whether a dose of 2 g cefoxitin as a prophylactic agent in patients undergoing elective colorectal surgery is able to maintain free drug concentrations above the minimum inhibitory concentration of the microorganisms involved in surgical site infection.

Methods

This was a prospective study involving 56 patients electively undergoing rectal or colon surgery. All plasma concentration–time data were analyzed simultaneously using the population approach to estimate population pharmacokinetic parameters and study the influence of the subjects’ demographic characteristics, disease status, surgical procedure, and clinical laboratory values on the pharmacokinetic properties of cefoxitin.

Results

A one-compartment open model was chosen to describe plasma concentrations of cefoxitin. Since cefoxitin is eliminated almost entirely via the kidney, creatinine clearance was identified as a covariate of cefoxitin clearance. The relationship between total cefoxitin clearance (CL) and creatinine clearance (CLCR) was best described using a nonlinear model [CL = 11.5 × (CLCR/77)0.52]. The population apparent volume of distribution was 12 L. Computer simulations carried out to determine the probability to maintain free plasma concentrations above 8 mg/L (the concentration threshold for susceptible bacteria) 2 h after drug administration revealed that this probability decreased from 84% in patients with a CLCR of 40 mL/min to 28% in patients with a CLCR of 100 mL/min.

Conclusions

To ensure cefoxitin target concentrations during surgery, we recommend that cefoxitin be administered every 1.5 h in patients with a CLCR ≥60 mL/min and every hour if the CLCR is ≥100 mL/min. Administration by continuous infusion preceded by a bolus injection should also be considered.

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Abbreviations

CL:

Total cefoxitin clearance

CLCR :

Creatinine clearance

FOCE:

First-order conditional estimation

npde:

Normalized prediction distribution errors

OFV:

Objective function value

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Acknowledgments

This work was supported by Caja Vital Kutxa and by the Departamento de Educación, Universidades e Investigación (IT341-10), Gobierno Vasco, Spain. Silvia Vázquez acknowledges the grant from the Departamento de Sanidad, Gobierno Vasco, Spain.

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Authors and Affiliations

  1. Laboratory of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of the Basque Country, Paseo de la Universidad 7, 01006, Vitoria-Gasteiz, Spain

    Arantxazu Isla, María Ángeles Solinís & Alicia Rodríguez Gascón

  2. Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Navarra, Pamplona, Spain

    Iñaki F. Trocóniz

  3. General and Digestive Surgery Unit, Santiago Hospital, Vitoria-Gasteiz, Spain

    Ignacio López de Tejada & Jesús Muriel López

  4. Microbiology Unit, Santiago Hospital, Vitoria, Spain

    Silvia Vázquez & Andrés Canut

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  1. Arantxazu Isla
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  2. Iñaki F. Trocóniz
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  8. Alicia Rodríguez Gascón
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Correspondence to Alicia Rodríguez Gascón.

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Isla, A., Trocóniz, I.F., de Tejada, I.L. et al. Population pharmacokinetics of prophylactic cefoxitin in patients undergoing colorectal surgery. Eur J Clin Pharmacol 68, 735–745 (2012). https://doi.org/10.1007/s00228-011-1206-1

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  • DOI: https://doi.org/10.1007/s00228-011-1206-1

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