The effects of yohimbine on the pharmacokinetic parameters of detomidine in the horse
Article first published online: 8 MAR 2012
© 2012 The Authors. Veterinary Anaesthesia and Analgesia. © 2012 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists
Veterinary Anaesthesia and Analgesia
Volume 39, Issue 3, pages 221–229, May 2012
How to Cite
Knych, H. K., Steffey, E. P. and Stanley, S. D. (2012), The effects of yohimbine on the pharmacokinetic parameters of detomidine in the horse. Veterinary Anaesthesia and Analgesia, 39: 221–229. doi: 10.1111/j.1467-2995.2011.00690.x
- Issue published online: 24 APR 2012
- Article first published online: 8 MAR 2012
- Received 1 October 2010; accepted 27 January 2011.
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 ± 56 kg.
Methods Three dose regimens were employed in the current study. 1) 0.03 mg kg−1 detomidine IV (D), 2) 0.2 mg kg−1 yohimbine IV (Y) and 3) 0.03 mg kg−1 detomidine IV followed 15 minutes later by 0.2 mg kg−1 yohimbine IV (DY). Each horse received all three dose regimens with a minimum of 1 week 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 129.9 ng mL−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 (173.9 ng mL−1) to DY (289.8 ng mL−1). Both the Cl and Vd for yohimbine were significantly less (6.8 mL minute−1 kg−1 (Cl) and 1.7 L kg−1 (Vd)) for the DY as compared to the Y treatments (13.9 mL minute−1 kg−1 (Cl) and 2.7 L kg−1 (Vd)). Plasma concentrations were below the limit of quantitation (0.05 and 0.5 ng mL−1) by 18 hours 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.