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.
  
  
  METHODS
  Randomized crossover design.
  
  
  METHODS
  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 V(d) for yohimbine were significantly less (6.8 mL minute(-1) kg(-1) (Cl) and 1.7 L kg(-1) (V(d) )) for the DY as compared to the Y treatments (13.9 mL minute(-1) kg(-1) (Cl) and 2.7 L kg(-1) (V(d))). Plasma concentrations were below the limit of quantitation (0.05 and 0.5 ng mL(-1)) by 18 hours for both detomidine and yohimbine.
  
  
  CONCLUSIONS
  The Cl and V(d) 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.
authors.affiliation: K.L. Maddy Equine Analytical Chemistry Laboratory, School of Veterinary Medicine, University of California, Davis, CA 95616, USA. hkknych@ucdavis.edu
authors.forename: Heather K
authors.initials: HK
authors.lastname: Knych
authors.forename: Eugene P
authors.initials: EP
authors.lastname: Steffey
authors.forename: Scott D
authors.initials: SD
authors.lastname: Stanley
mesh_terms: D058669:Adrenergic alpha-2 Receptor Antagonists / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000818:Animals; D019540:Area Under Curve; D018592:Cross-Over Studies; D004359:Drug Therapy, Combination; D005260:Female; D006207:Half-Life; D006736:Horses / Q000097:blood*; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D007093:Imidazoles / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D015016:Yohimbine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D058669:Adrenergic alpha-2 Receptor Antagonists; D006993:Hypnotics and Sedatives; D007093:Imidazoles; D015016:Yohimbine; C041255:detomidine