The effects of yohimbine on the pharmacokinetic parameters of detomidine in the horse

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Abstract

Objective To describe the pharmacokinetics of detomidine and yohimbine when administered in combination. Study design Randomized crossover design. Animals Nine healthy adult horses aged 9±4 years and weighing of 561±56kg. Methods Three dose regimens were employed in the current study. 1) 0.03mgkg-1 detomidine IV (D), 2) 0.2mgkg-1 yohimbine IV (Y) and 3) 0.03mgkg-1 detomidine IV followed 15minutes later by 0.2mgkg-1 yohimbine IV (DY). Each horse received all three dose regimens with a minimum of 1week in between subsequent regimens. Blood samples were obtained and plasma analyzed for detomidine and yohimbine concentrations by liquid chromatography-mass spectrometry. Data were analyzed using both non-compartmental and compartmental analysis. Results The maximum measured detomidine concentrations were 76.0 and 129.9ngmL-1 for the D and DY treatments, respectively. Systemic clearance and volume of distribution of detomidine were not significantly different for either treatment. There was a significant increase in the maximum measured yohimbine plasma concentrations from Y (173.9ngmL-1) to DY (289.8ngmL-1). Both the Cl and Vd for yohimbine were significantly less (6.8mLminute-1kg-1 (Cl) and 1.7Lkg-1 (Vd)) for the DY as compared to the Y treatments (13.9 mLminute-1kg-1 (Cl) and 2.7Lkg-1 (Vd)). Plasma concentrations were below the limit of quantitation (0.05 and 0.5ngmL-1) by 18hours for both detomidine and yohimbine. Conclusion and clinical relevance The Cl and Vd of yohimbine were affected by prior administration of detomidine. The elimination half life of yohimbine remained unaffected when administered subsequent to detomidine. However, the increased plasma concentrations in the presence of detomidine has the potential to cause untoward effects and therefore further studies to assess the physiologic effects of this combination of drugs are warranted.

Original languageEnglish (US)
Pages (from-to)221-229
Number of pages9
JournalVeterinary Anaesthesia and Analgesia
Volume39
Issue number3
DOIs
StatePublished - Mar 2012

Fingerprint

detomidine
yohimbine
Yohimbine
pharmacokinetics
Horses
Pharmacokinetics
horses
combination drug therapy
Drug Combinations
dosage
Liquid Chromatography
Cross-Over Studies
liquid chromatography
half life
Half-Life
Mass Spectrometry
Therapeutics
experimental design
mass spectrometry

Keywords

  • Detomidine
  • Equine
  • Yohimbine

ASJC Scopus subject areas

  • veterinary(all)

Cite this

@article{1a7e40f284b249749388ecb427a749ee,
title = "The effects of yohimbine on the pharmacokinetic parameters of detomidine in the horse",
abstract = "Objective To describe the pharmacokinetics of detomidine and yohimbine when administered in combination. Study design Randomized crossover design. Animals Nine healthy adult horses aged 9±4 years and weighing of 561±56kg. Methods Three dose regimens were employed in the current study. 1) 0.03mgkg-1 detomidine IV (D), 2) 0.2mgkg-1 yohimbine IV (Y) and 3) 0.03mgkg-1 detomidine IV followed 15minutes later by 0.2mgkg-1 yohimbine IV (DY). Each horse received all three dose regimens with a minimum of 1week in between subsequent regimens. Blood samples were obtained and plasma analyzed for detomidine and yohimbine concentrations by liquid chromatography-mass spectrometry. Data were analyzed using both non-compartmental and compartmental analysis. Results The maximum measured detomidine concentrations were 76.0 and 129.9ngmL-1 for the D and DY treatments, respectively. Systemic clearance and volume of distribution of detomidine were not significantly different for either treatment. There was a significant increase in the maximum measured yohimbine plasma concentrations from Y (173.9ngmL-1) to DY (289.8ngmL-1). Both the Cl and Vd for yohimbine were significantly less (6.8mLminute-1kg-1 (Cl) and 1.7Lkg-1 (Vd)) for the DY as compared to the Y treatments (13.9 mLminute-1kg-1 (Cl) and 2.7Lkg-1 (Vd)). Plasma concentrations were below the limit of quantitation (0.05 and 0.5ngmL-1) by 18hours for both detomidine and yohimbine. Conclusion and clinical relevance The Cl and Vd of yohimbine were affected by prior administration of detomidine. The elimination half life of yohimbine remained unaffected when administered subsequent to detomidine. However, the increased plasma concentrations in the presence of detomidine has the potential to cause untoward effects and therefore further studies to assess the physiologic effects of this combination of drugs are warranted.",
keywords = "Detomidine, Equine, Yohimbine",
author = "Knych, {Heather K} and Eugene Steffey and Stanley, {Scott D}",
year = "2012",
month = "3",
doi = "10.1111/j.1467-2995.2011.00690.x",
language = "English (US)",
volume = "39",
pages = "221--229",
journal = "Veterinary Anaesthesia and Analgesia",
issn = "1467-2987",
publisher = "Wiley-Blackwell",
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}

TY - JOUR

T1 - The effects of yohimbine on the pharmacokinetic parameters of detomidine in the horse

AU - Knych, Heather K

AU - Steffey, Eugene

AU - Stanley, Scott D

PY - 2012/3

Y1 - 2012/3

N2 - Objective To describe the pharmacokinetics of detomidine and yohimbine when administered in combination. Study design Randomized crossover design. Animals Nine healthy adult horses aged 9±4 years and weighing of 561±56kg. Methods Three dose regimens were employed in the current study. 1) 0.03mgkg-1 detomidine IV (D), 2) 0.2mgkg-1 yohimbine IV (Y) and 3) 0.03mgkg-1 detomidine IV followed 15minutes later by 0.2mgkg-1 yohimbine IV (DY). Each horse received all three dose regimens with a minimum of 1week in between subsequent regimens. Blood samples were obtained and plasma analyzed for detomidine and yohimbine concentrations by liquid chromatography-mass spectrometry. Data were analyzed using both non-compartmental and compartmental analysis. Results The maximum measured detomidine concentrations were 76.0 and 129.9ngmL-1 for the D and DY treatments, respectively. Systemic clearance and volume of distribution of detomidine were not significantly different for either treatment. There was a significant increase in the maximum measured yohimbine plasma concentrations from Y (173.9ngmL-1) to DY (289.8ngmL-1). Both the Cl and Vd for yohimbine were significantly less (6.8mLminute-1kg-1 (Cl) and 1.7Lkg-1 (Vd)) for the DY as compared to the Y treatments (13.9 mLminute-1kg-1 (Cl) and 2.7Lkg-1 (Vd)). Plasma concentrations were below the limit of quantitation (0.05 and 0.5ngmL-1) by 18hours for both detomidine and yohimbine. Conclusion and clinical relevance The Cl and Vd of yohimbine were affected by prior administration of detomidine. The elimination half life of yohimbine remained unaffected when administered subsequent to detomidine. However, the increased plasma concentrations in the presence of detomidine has the potential to cause untoward effects and therefore further studies to assess the physiologic effects of this combination of drugs are warranted.

AB - Objective To describe the pharmacokinetics of detomidine and yohimbine when administered in combination. Study design Randomized crossover design. Animals Nine healthy adult horses aged 9±4 years and weighing of 561±56kg. Methods Three dose regimens were employed in the current study. 1) 0.03mgkg-1 detomidine IV (D), 2) 0.2mgkg-1 yohimbine IV (Y) and 3) 0.03mgkg-1 detomidine IV followed 15minutes later by 0.2mgkg-1 yohimbine IV (DY). Each horse received all three dose regimens with a minimum of 1week in between subsequent regimens. Blood samples were obtained and plasma analyzed for detomidine and yohimbine concentrations by liquid chromatography-mass spectrometry. Data were analyzed using both non-compartmental and compartmental analysis. Results The maximum measured detomidine concentrations were 76.0 and 129.9ngmL-1 for the D and DY treatments, respectively. Systemic clearance and volume of distribution of detomidine were not significantly different for either treatment. There was a significant increase in the maximum measured yohimbine plasma concentrations from Y (173.9ngmL-1) to DY (289.8ngmL-1). Both the Cl and Vd for yohimbine were significantly less (6.8mLminute-1kg-1 (Cl) and 1.7Lkg-1 (Vd)) for the DY as compared to the Y treatments (13.9 mLminute-1kg-1 (Cl) and 2.7Lkg-1 (Vd)). Plasma concentrations were below the limit of quantitation (0.05 and 0.5ngmL-1) by 18hours for both detomidine and yohimbine. Conclusion and clinical relevance The Cl and Vd of yohimbine were affected by prior administration of detomidine. The elimination half life of yohimbine remained unaffected when administered subsequent to detomidine. However, the increased plasma concentrations in the presence of detomidine has the potential to cause untoward effects and therefore further studies to assess the physiologic effects of this combination of drugs are warranted.

KW - Detomidine

KW - Equine

KW - Yohimbine

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