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Eur J Clin Pharmacol. 2015 Dec;71(12):1501-8. doi: 10.1007/s00228-015-1948-2. Epub 2015 Sep 26.

Dexmedetomidine pharmacokinetics in the obese.

Author information

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. licorti@med.puc.cl.
2
Department of Anaesthesiology, University of Auckland, Auckland, New Zealand.
3
Department of Pharmacology & Clinical Pharmacology, University of Auckland, Auckland, New Zealand.
4
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.
5
Laboratorio Clínico, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.

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.

KEYWORDS:

Dexmedetomidine; Fat free mass; Obese

PMID:
26407689
DOI:
10.1007/s00228-015-1948-2
[Indexed for MEDLINE]

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