Plasma concentrations, behavioural and physiological effects following intravenous and intramuscular detomidine in horses

• Published in: Equine veterinary journal 2009-11, Vol.41 (8), p.772-777
• Main Authors: Mama, K.R, Grimsrud, K, Snell, T, Stanley, S
• Format: Article
• Language: English
• Subjects: analgesia; animal behavior; Animals; blood chemistry; blood plasma; clinical pharmacology; Cross-Over Studies; detomidine; dosage; Dose-Response Relationship, Drug; Female; heart rate; Heart Rate - drug effects; horse; Horses; Hypnotics and Sedatives - administration & dosage; Hypnotics and Sedatives - blood; Hypnotics and Sedatives - pharmacokinetics; Hypnotics and Sedatives - pharmacology; Imidazoles - administration & dosage; Imidazoles - blood; Imidazoles - pharmacokinetics; Imidazoles - pharmacology; Injections, Intramuscular; Injections, Intravenous; intramuscular injection; intravenous injection; Male; metabolites; Pain - prevention & control; Pain Measurement - veterinary; pharmacokinetics; pharmacology; Respiration - drug effects; sedation; sedative; Time Factors
• ISSN: 0425-1644; 2042-3306
• DOI: 10.2746/042516409X421624

Summary Reasons for performing study: 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. Objectives: 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. Hypothesis: 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 μg/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. Potential relevance: Results support a significant influence of route of administration on desirable and undesirable drug effects that influence case management.