title: Plasma concentrations, behavioural and physiological effects following intravenous and intramuscular detomidine in horses.
abstract: BACKGROUND
  Detomidine hydrochloride is used to provide sedation, muscle relaxation and analgesia in horses, but a lack of information pertaining to plasma concentration has limited the ability to correlate drug concentration with effect.
  
  
  OBJECTIVE
  To build on previous information and assess detomidine for i.v. and i.m. use in horses by simultaneously assessing plasma drug concentrations, physiological parameters and behavioural characteristics.
  
  
  OBJECTIVE
  Systemic effects would be seen following i.m. and i.v. detomidine administration and these effects would be positively correlated with plasma drug concentrations.
  
  
  METHODS
  Behavioural (e.g. head position) and physiological (e.g. heart rate) responses were recorded at fixed time points from 4 min to 24 h after i.m. or i.v. detomidine (30 microg/kg bwt) administration to 8 horses. Route of administration was assigned using a balanced crossover design. Blood was sampled at predetermined time points from 0.5 min to 48 h post administration for subsequent detomidine concentration measurements using liquid chromatography-mass spectrometry. Data were summarised as mean +/- s.d. for subsequent analysis of variance for repeated measures.
  
  
  RESULTS
  Plasma detomidine concentration peaked earlier (1.5 min vs. 1.5 h) and was significantly higher (105.4 +/- 71.6 ng/ml vs. 6.9 +/- 1.4 ng/ml) after i.v. vs. i.m. administration. Physiological and behavioural changes were of a greater magnitude and observed at earlier time points for i.v. vs. i.m. groups. For example, head position decreased from an average of 116 cm in both groups to a low value 35 +/- 23 cm from the ground 10 min following i.v. detomidine and to 64 +/- 24 cm 60 min after i.m. detomidine. Changes in heart rate followed a similar pattern; low value of 17 beats/min 10 min after i.v. administration and 29 beats/min 30 min after i.m. administration.
  
  
  CONCLUSIONS
  Plasma drug concentration and measured effects were correlated positively and varied with route of administration following a single dose of detomidine.
  
  
  CONCLUSIONS
  Results support a significant influence of route of administration on desirable and undesirable drug effects that influence case management.
authors.affiliation: Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado 80523, USA.
authors.forename: K R
authors.initials: KR
authors.lastname: Mama
authors.forename: K
authors.initials: K
authors.lastname: Grimsrud
authors.forename: T
authors.initials: T
authors.lastname: Snell
authors.forename: S
authors.initials: S
authors.lastname: Stanley
mesh_terms: D000818:Animals; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006736:Horses; D006993:Hypnotics and Sedatives / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D007093:Imidazoles / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D008297:Male; D010146:Pain / Q000517:prevention & control; D010147:Pain Measurement / Q000662:veterinary; D012119:Respiration / Q000187:drug effects; D013997:Time Factors
chemical_list: D006993:Hypnotics and Sedatives; D007093:Imidazoles; C041255:detomidine