Detomidine is classified as a class 3 foreign substance by the Association of Racing Commissioners International, with any detectable concentration in a horse during racing competition considered a violation. Recently, a novel gel formulation has become commercially available. Because detomidine is commonly used in veterinary medicine and this gel formulation has the potential to be used for a number of minor veterinary and nonveterinary procedures, establishment of appropriate withdrawal guidelines is necessary.
Detomidine is an α2-adrenergic receptor agonist used commonly in veterinary medicine for procedures requiring sedation, chemical restraint, or analgesia. The pharmacokinetic and pharmacodynamic effects of detomidine after IV or IM administration to horses have been described.1–4 Pharmacokinetic studies1,3,4 indicate that detomidine is rapidly distributed and quickly metabolized and eliminated following parenteral administration. Physiologic effects, such as changes in head height and heart rate, are rapid and dose dependent.2 Investigators in 1 study2 reported significant changes in head position at 10 and 30 minutes after IV and IM administration, respectively, with changes in heart rate first detected at 10 minutes after IV administration and persisting for as long as 90 minutes.
Absorption of drugs following sublingual administration is generally rapid because of the large network of capillaries and lymphatic vessels located under the tongue. Furthermore, high systemic concentrations can be achieved because sublingual administration allows drugs to pass directly into the systemic circulation, thus avoiding immediate destruction by gastric acid, presystemic metabolism by the wall of the gastrointestinal tract, or first-pass effects frequently associated with oral administration. This is of particular importance for drugs that are subject to first-pass elimination, such as detomidine. To the author's knowledge, there are 2 reports5,6 in which investigators describe sublingual administration of detomidine. In one of those studies,5 investigators evaluated the effectiveness of detomidine administered sublingually to ponies by use of an injectable formulation administered under the tongue. The authors concluded that sublingual administration of detomidine at a dose of 0.04 mg/kg results in a useful degree of sedation in horses, provided adequate time (45 minutes) is allowed for maximal effects. The novel detomidine gel formulation provides an alternative for sublingual administration of the injectable formulation. Therefore, the purpose of the study reported here was to characterize the pharmacokinetics of the novel detomidine gel when administered sublingually in horses in accordance with label instructions and obtain sufficient information on which to establish appropriate withdrawal guidelines prior to performance events, such as racing. Additionally, a number of pharmacodynamic properties of detomidine gel were evaluated, including extent of sedation, as determined by the chin-to-ground distance and behavioral observations, and effects on heart rate and rhythm. Physiologic effects observed following sublingual administration were then compared with those reported for IV and IM administration in another study2 conducted by our laboratory group.
Area under the curve
Maximal plasma concentration
Limit of detection
Limit of quantitation
Time of maximal plasma concentration
Horses used in the study were provided by Ellen Jackson, Victory Rose Thoroughbreds, Vacaville, Calif.
Dormosedan gel, Pfizer Animal Health, New York, NY.
Forrest Medical, East Syracuse, NY.
SAS, version 9.2, SAS Institute Inc, Cary, NC.
TSQ Vantage, Thermo Scientific, San Jose, Calif.
TLX4, Thermo Fisher Scientific, Franklin, Mass.
ACE column, Mac-Mod, Chadds Ford, Pa.
LCQuan software, Thermo Scientific, San Jose, Calif.
WinNonlin, version 5.2, Pharsight Corp, Mountain View, Calif.
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