The bioavailability of medetomidine in eight sheep following oesophageal administration

Res Vet Sci. 2015 Dec:103:137-42. doi: 10.1016/j.rvsc.2015.09.014. Epub 2015 Sep 25.

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).

Keywords: Analgesia; Medetomidine; Oral administration; Osmotic pump; Pain; Sheep.

MeSH terms

  • Administration, Oral
  • Adrenergic alpha-2 Receptor Agonists / pharmacokinetics
  • Analgesics / pharmacokinetics*
  • Animals
  • Biological Availability
  • Cross-Over Studies
  • Female
  • Male
  • Medetomidine / pharmacokinetics*
  • Sheep, Domestic / metabolism*

Substances

  • Adrenergic alpha-2 Receptor Agonists
  • Analgesics
  • Medetomidine