title: Pharmacokinetics and pharmacodynamics of detomidine following sublingual administration to horses.
abstract: OBJECTIVE
  To characterize pharmacokinetics and pharmacodynamics of detomidine gel administered sublingually in accordance with label instructions to establish appropriate withdrawal guidelines for horses before competition.
  
  
  METHODS
  12 adult racehorses.
  
  
  METHODS
  Horses received a single sublingual administration of 0.04 mg of detomidine/kg. Blood samples were collected before and up to 72 hours after drug administration. Urine samples were collected for 5 days after detomidine administration. Plasma and urine samples were analyzed via liquid chromatography-mass spectrometry, and resulting data were analyzed by use of noncompartmental analysis. Chin-to-ground distance, heart rate and rhythm, glucose concentration, PCV, and plasma protein concentration were also assessed following detomidine administration.
  
  
  RESULTS
  Mean ± SD terminal elimination half-life of detomidine was 1.5 ± 1 hours. Metabolite concentrations were below the limit of detection (0.02, 0.1, and 0.5 ng/mL for detomidine, carboxydetomidine, and hydroxydetomidine, respectively) in plasma by 24 hours. Concentrations of detomidine and its metabolites were below the limit of detection (0.05 ng/mL for detomidine and 0.10 ng/mL for carboxydetomidine and hydroxydetomidine) in urine by 3 days. All horses had various degrees of sedation after detomidine administration. Time of onset was ≤ 40 minutes, and duration of sedation was approximately 2 hours. Significant decreases, relative to values at time 0, were detected for chin-to-ground distance and heart rate. There was an increased incidence and exacerbation of preexisting atrioventricular blocks after detomidine administration.
  
  
  CONCLUSIONS
  A 48-hour and 3-day withdrawal period for detection in plasma and urine samples, respectively, should be adopted for sublingual administration of detomidine gel.
authors.affiliation: K. L. Maddy Equine Analytical Chemistry Laboratory, Department of Veterinary Molecular Biosciences, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616, USA. hkknych@ucdavis.edu
authors.forename: Heather K
authors.initials: HK
authors.lastname: Dimaio Knych
authors.forename: Scott D
authors.initials: SD
authors.lastname: Stanley
mesh_terms: D000286:Administration, Sublingual; D000704:Analysis of Variance; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001798:Blood Proteins / Q000032:analysis; D002853:Chromatography, Liquid / Q000662:veterinary; D006207:Half-Life; D006339:Heart Rate / Q000187:drug effects; D006736:Horses / Q000378:metabolism*; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D007093:Imidazoles / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D008297:Male; D013058:Mass Spectrometry / Q000662:veterinary; D013997:Time Factors
chemical_list: D001786:Blood Glucose; D001798:Blood Proteins; D006993:Hypnotics and Sedatives; D007093:Imidazoles; C041255:detomidine