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Dexmedetomidine pharmacokinetics in the obese

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

Abstract

Purpose

This study aims to characterize the influence of body weight and composition on the pharmacokinetics of dexmedetomidine.

Methods

Twenty obese patients and 20 non-obese patients scheduled for elective laparoscopic surgery were given dexmedetomidine infusion schemes. Venous blood samples were taken during and after dexmedetomidine administration. Population pharmacokinetic modeling was undertaken to investigate fat free mass (FFM) and normal fat mass (NFM) as size descriptors of volumes and clearances using non-linear mixed effects modeling. NFM partitions total body weight into FFM and fat mass calculated from total body weight (TBW) minus FFM. The relative influence of fat mass compared to FFM is described by the fraction of fat mass that makes fat equivalent to FFM (Ffat).

Results

Theory-based allometric scaling using FFM best described weight and body composition differences in clearances and volumes A negative effect of fat mass of with an exponential parameter of −0.00541/kg (95 % CI −0.0118 to −0.00246) was estimated for clearance which indicates increased fat mass is associated with impairment of clearance.

Conclusions

The use of theory-based allometry with predictions of fat free mass has been able to separate the influences of weight and body composition and indicates that size-normalized clearance of dexmedetomidine is impaired in patients who are obese.

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Acknowledgments

This study was funded by FONDECYT (Fondo Nacional de Desarrollo Científico y Tecnológico), Project Number 1120583.

Author contributions

Luis I. Cortínez helped design the study, conduct the study, analyze the data, and write the manuscript; Brian J. Anderson helped to analyze the data and write the manuscript; Nick HG Holford helped to analyze the data and write the manuscript; Valentina Puga helped design the study and conduct the study; Natalia De la Fuente helped design the study and conduct the study; Hernán Auad helped analyze the data; Sandra Solari helped design the study, analyze the data, and write the manuscript; Fidel A. Allende helped analyze the data and write the manuscript; Mauricio Ibacache helped design the study, conduct the study, and write the manuscript.

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Authors and Affiliations

  1. Departamento de Anestesiología and Laboratorio Clínico, Escuela de Medicina, Hospital Clínico U. Católica, Pontificia Universidad Católica de Chile, Marcoleta 367, PO Box: 114-D, Santiago, Chile

    Luis I. Cortínez, Valentina Puga, Natalia de la Fuente, Hernán Auad & Mauricio Ibacache

  2. Department of Anaesthesiology, University of Auckland, Auckland, New Zealand

    Brian J. Anderson

  3. Department of Pharmacology & Clinical Pharmacology, University of Auckland, Auckland, New Zealand

    Nick H. G. Holford

  4. Laboratorio Clínico, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile

    Sandra Solari & Fidel A. Allende

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  1. Luis I. Cortínez
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Corresponding author

Correspondence to Luis I. Cortínez.

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Cortínez, L.I., Anderson, B.J., Holford, N.H.G. et al. Dexmedetomidine pharmacokinetics in the obese. Eur J Clin Pharmacol 71, 1501–1508 (2015). https://doi.org/10.1007/s00228-015-1948-2

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  • DOI: https://doi.org/10.1007/s00228-015-1948-2

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