The Pharmacokinetics of Medetomidine Administered Subcutaneously during Isoflurane Anaesthesia in Sprague-Dawley Rats

Anaesthetic protocols involving the combined use of a sedative agent, medetomidine, and an anaesthetic agent, isoflurane, are increasingly being used in functional magnetic resonance imaging (fMRI) studies of the rodent brain. Despite the popularity of this combination, a standardised protocol for t...

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Main Authors: Leila T. Kint, Bhedita J. Seewoo, Timothy H. Hyndman, Michael W. Clarke, Scott H. Edwards, Jennifer Rodger, Kirk W. Feindel, Gabrielle C. Musk
Format: Article
Language:English
Published: MDPI AG 2020-06-01
Series:Animals
Subjects:
Online Access:https://www.mdpi.com/2076-2615/10/6/1050
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author Leila T. Kint
Bhedita J. Seewoo
Timothy H. Hyndman
Michael W. Clarke
Scott H. Edwards
Jennifer Rodger
Kirk W. Feindel
Gabrielle C. Musk
author_facet Leila T. Kint
Bhedita J. Seewoo
Timothy H. Hyndman
Michael W. Clarke
Scott H. Edwards
Jennifer Rodger
Kirk W. Feindel
Gabrielle C. Musk
author_sort Leila T. Kint
collection DOAJ
description Anaesthetic protocols involving the combined use of a sedative agent, medetomidine, and an anaesthetic agent, isoflurane, are increasingly being used in functional magnetic resonance imaging (fMRI) studies of the rodent brain. Despite the popularity of this combination, a standardised protocol for the combined use of medetomidine and isoflurane has not been established, resulting in inconsistencies in the reported use of these drugs. This study investigated the pharmacokinetic detail required to standardise the use of medetomidine and isoflurane in rat brain fMRI studies. Using mass spectrometry, serum concentrations of medetomidine were determined in Sprague-Dawley rats during medetomidine and isoflurane anaesthesia. The serum concentration of medetomidine for administration with 0.5% (vapouriser setting) isoflurane was found to be 14.4 ng/mL (±3.0 ng/mL). The data suggests that a steady state serum concentration of medetomidine when administered with 0.5% (vapouriser setting) isoflurane can be achieved with an initial subcutaneous (SC) dose of 0.12 mg/kg of medetomidine followed by a 0.08 mg/kg/h SC infusion of medetomidine. Consideration of these results for future studies will facilitate standardisation of medetomidine and isoflurane anaesthetic protocols during fMRI data acquisition.
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spelling doaj.art-043c338c732d45e8950375bfe98c3f722023-11-20T04:13:59ZengMDPI AGAnimals2076-26152020-06-01106105010.3390/ani10061050The Pharmacokinetics of Medetomidine Administered Subcutaneously during Isoflurane Anaesthesia in Sprague-Dawley RatsLeila T. Kint0Bhedita J. Seewoo1Timothy H. Hyndman2Michael W. Clarke3Scott H. Edwards4Jennifer Rodger5Kirk W. Feindel6Gabrielle C. Musk7Faculty of Health and Medical Sciences, The University of Western Australia, Perth 6009, AustraliaCentre for Microscopy, Characterisation and Analysis, Research Infrastructure Centres, The University of Western Australia, Perth 6009, AustraliaSchool of Veterinary Medicine, Murdoch University, Perth 6150, AustraliaMetabolomics Australia, Centre for Microscopy, Characterisation and Analysis, The University of Western Australia, Perth 6009, AustraliaSchool of Animal Veterinary Sciences, Charles Sturt University, Wagga Wagga 2650, AustraliaExperimental and Regenerative Neurosciences, School of Biological Sciences, The University of Western Australia, Perth 6009, AustraliaCentre for Microscopy, Characterisation and Analysis, Research Infrastructure Centres, The University of Western Australia, Perth 6009, AustraliaFaculty of Health and Medical Sciences, The University of Western Australia, Perth 6009, AustraliaAnaesthetic protocols involving the combined use of a sedative agent, medetomidine, and an anaesthetic agent, isoflurane, are increasingly being used in functional magnetic resonance imaging (fMRI) studies of the rodent brain. Despite the popularity of this combination, a standardised protocol for the combined use of medetomidine and isoflurane has not been established, resulting in inconsistencies in the reported use of these drugs. This study investigated the pharmacokinetic detail required to standardise the use of medetomidine and isoflurane in rat brain fMRI studies. Using mass spectrometry, serum concentrations of medetomidine were determined in Sprague-Dawley rats during medetomidine and isoflurane anaesthesia. The serum concentration of medetomidine for administration with 0.5% (vapouriser setting) isoflurane was found to be 14.4 ng/mL (±3.0 ng/mL). The data suggests that a steady state serum concentration of medetomidine when administered with 0.5% (vapouriser setting) isoflurane can be achieved with an initial subcutaneous (SC) dose of 0.12 mg/kg of medetomidine followed by a 0.08 mg/kg/h SC infusion of medetomidine. Consideration of these results for future studies will facilitate standardisation of medetomidine and isoflurane anaesthetic protocols during fMRI data acquisition.https://www.mdpi.com/2076-2615/10/6/1050functional MRIrat anaesthesiarefinement
spellingShingle Leila T. Kint
Bhedita J. Seewoo
Timothy H. Hyndman
Michael W. Clarke
Scott H. Edwards
Jennifer Rodger
Kirk W. Feindel
Gabrielle C. Musk
The Pharmacokinetics of Medetomidine Administered Subcutaneously during Isoflurane Anaesthesia in Sprague-Dawley Rats
Animals
functional MRI
rat anaesthesia
refinement
title The Pharmacokinetics of Medetomidine Administered Subcutaneously during Isoflurane Anaesthesia in Sprague-Dawley Rats
title_full The Pharmacokinetics of Medetomidine Administered Subcutaneously during Isoflurane Anaesthesia in Sprague-Dawley Rats
title_fullStr The Pharmacokinetics of Medetomidine Administered Subcutaneously during Isoflurane Anaesthesia in Sprague-Dawley Rats
title_full_unstemmed The Pharmacokinetics of Medetomidine Administered Subcutaneously during Isoflurane Anaesthesia in Sprague-Dawley Rats
title_short The Pharmacokinetics of Medetomidine Administered Subcutaneously during Isoflurane Anaesthesia in Sprague-Dawley Rats
title_sort pharmacokinetics of medetomidine administered subcutaneously during isoflurane anaesthesia in sprague dawley rats
topic functional MRI
rat anaesthesia
refinement
url https://www.mdpi.com/2076-2615/10/6/1050
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