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The intravenous pharmacokinetics of butorphanol and detomidine dosed in combination compared with individual dose administrations to exercised horses

Paine, Stuart W; Bright, Jane; Scarth, James P; Hincks, Pamela R; Pearce, Clive M; Hannan, Colette; Machnik, Marc; Hillyer, Lynn

The intravenous pharmacokinetics of butorphanol and detomidine dosed in combination compared with individual dose administrations to exercised horses Thumbnail


Authors

STUART PAINE Stuart.Paine@nottingham.ac.uk
Professor of Pharmacometrics

Jane Bright

James P Scarth

Pamela R Hincks

Clive M Pearce

Colette Hannan

Marc Machnik

Lynn Hillyer



Abstract

In equine and racing practice, detomidine and butorphanol are commonly used in combination for their sedative properties. The aim of the study was to produce detection times to better inform European veterinary surgeons, so that both drugs can be used appropriately under regulatory rules. Three independent groups of 7, 8 and 6 horses, respectively, were given either a single intravenous administration of butorphanol (100µg/kg), a single intravenous administration of detomidine (10µg/kg) or a combination of both at 25 (butorphanol) and 10 (detomidine) µg/kg. Plasma and urine concentrations of butorphanol, detomidine and 3-hydroxydetomidine at predetermined time points were measured by liquid chromatography–tandem mass spectrometry (LC-MS/MS). The intravenous pharmacokinetics of butorphanol dosed individually compared with co-administration with detomidine had approximately a twofold larger clearance (646±137 vs. 380±86mlhr−1kg−1) but similar terminal half-life (5.21±1.56 vs. 5.43±0.44hr). Pseudo-steady-state urine to plasma butorphanol concentration ratios were 730 and 560, respectively. The intravenous pharmacokinetics of detomidine dosed as a single administration compared with co-administration with butorphanol had similar clearance (3,278±1,412 vs. 2,519±630mlhr−1kg−1) but a slightly shorter terminal half-life (0.57±0.06 vs. 0.70±0.11hr). Pseudo-steady-state urine to plasma detomidine concentration ratios are 4 and 8, respectively. The 3-hydroxy metabolite of detomidine was detected for at least 35hr in urine from both the single and co-administrations. Detection times of 72 and 48hr are recommended for the control of butorphanol and detomidine, respectively, in horseracing and equestrian competitions.

Citation

Paine, S. W., Bright, J., Scarth, J. P., Hincks, P. R., Pearce, C. M., Hannan, C., …Hillyer, L. (2020). The intravenous pharmacokinetics of butorphanol and detomidine dosed in combination compared with individual dose administrations to exercised horses. Journal of Veterinary Pharmacology and Therapeutics, 43(2), 162-170. https://doi.org/10.1111/jvp.12838

Journal Article Type Article
Acceptance Date Jan 6, 2020
Online Publication Date Feb 3, 2020
Publication Date 2020-03
Deposit Date Jan 29, 2020
Publicly Available Date Mar 28, 2024
Journal Journal of Veterinary Pharmacology and Therapeutics
Print ISSN 0140-7783
Electronic ISSN 1365-2885
Publisher Wiley
Peer Reviewed Peer Reviewed
Volume 43
Issue 2
Pages 162-170
DOI https://doi.org/10.1111/jvp.12838
Keywords butorphanol; detection time; detomidine; drug-drug interactions; horse; pharmacokinetics
Public URL https://nottingham-repository.worktribe.com/output/3828807
Publisher URL https://onlinelibrary.wiley.com/doi/full/10.1111/jvp.12838
Additional Information This is the peer reviewed version of the following article: Paine, SW, Bright, J, Scarth, JP, et al. The intravenous pharmacokinetics of butorphanol and detomidine dosed in combination compared with individual dose administrations to exercised horses. J vet Pharmacol Therap., which has been published in final form at https://onlinelibrary.w...full/10.1111/jvp.12838. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.

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