title: The bioavailability of medetomidine in eight sheep following oesophageal administration.
abstract: There is sound evidence that medetomidine is an effective analgesic for acute pain in sheep. In this study, 15 μg kg(-1) of medetomidine was administered intravenously, and into the oesophagus, in a cross-over study, using eight sheep. Following intravenous administration, medetomidine could be detected in the plasma of these sheep for 120-180 min but following oesophageal administration, medetomidine could not be detected in the plasma of any sheep at any of 17 time points over four days. It is suspected that this is due to high first pass metabolism in the liver. Consequently, we conclude that future studies investigating the use of analgesics in orally-administered osmotic pumps in sheep should consider higher doses of medetomidine (e.g. >100 μg kg(-1)), further investigations into the barriers of medetomidine bioavailability from the sheep gut, liver-bypass drug delivery systems, or other α2-adrenergic agonists (e.g. clonidine or xylazine).
authors.affiliation: School of Veterinary and Life Sciences, Murdoch University, Perth, Australia. Electronic address: t.hyndman@murdoch.edu.au.
authors.forename: Timothy H
authors.initials: TH
authors.lastname: Hyndman
authors.affiliation: School of Veterinary and Life Sciences, Murdoch University, Perth, Australia.
authors.forename: Gabrielle C
authors.initials: GC
authors.lastname: Musk
authors.affiliation: School of Veterinary and Life Sciences, Murdoch University, Perth, Australia; Scottish Centre for Production Animal Health and Food Safety, School of Veterinary Medicine, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Fraser R
authors.initials: FR
authors.lastname: Murdoch
authors.affiliation: School of Veterinary and Life Sciences, Murdoch University, Perth, Australia.
authors.forename: Garth L
authors.initials: GL
authors.lastname: Maker
authors.affiliation: Translational Research and Clinical Trials (TRACTs) Group, Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, 250 Princes Highway, Werribee, Victoria, Australia.
authors.forename: Ted
authors.initials: T
authors.lastname: Whittem
mesh_terms: D000284:Administration, Oral; D058647:Adrenergic alpha-2 Receptor Agonists / Q000493:pharmacokinetics; D000700:Analgesics / Q000493:pharmacokinetics*; D000818:Animals; D001682:Biological Availability; D018592:Cross-Over Studies; D005260:Female; D008297:Male; D020926:Medetomidine / Q000493:pharmacokinetics*; D034561:Sheep, Domestic / Q000378:metabolism*
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D000700:Analgesics; D020926:Medetomidine
keywords: Analgesia; Medetomidine; Oral administration; Osmotic pump; Pain; Sheep