Efficacy of sublingual administration of detomidine gel for sedation of horses undergoing veterinary and husbandry procedures under field conditions

Rachel B. Gardner BW Furlong and Associates, 101 Homestead Rd, Oldwick, NJ 08858.

Search for other papers by Rachel B. Gardner in
Current site
Google Scholar
PubMed
Close
 DVM, DACVIM
,
Gary W. White Sallisaw Equine Clinic, 213 N Shiloh St, Sallisaw, OK 74955.

Search for other papers by Gary W. White in
Current site
Google Scholar
PubMed
Close
 DVM
,
Deborah S. Ramsey Pfizer Animal Health, Veterinary Medicine Research & Development, 333 Portage Rd, Building 300, Kalamazoo, MI 49007.

Search for other papers by Deborah S. Ramsey in
Current site
Google Scholar
PubMed
Close
 DVM
,
Joseph F. Boucher Pfizer Animal Health, Veterinary Medicine Research & Development, 333 Portage Rd, Building 300, Kalamazoo, MI 49007.

Search for other papers by Joseph F. Boucher in
Current site
Google Scholar
PubMed
Close
 MS
,
W. Randal Kilgore Pfizer Animal Health, Veterinary Medicine Research & Development, 333 Portage Rd, Building 300, Kalamazoo, MI 49007.

Search for other papers by W. Randal Kilgore in
Current site
Google Scholar
PubMed
Close
 DVM
, and
Mirja K. Huhtinen Orion Corporation, Orion Pharma, Research and Development, Tengströminkatu 8, 20360 Turku, Finland.

Search for other papers by Mirja K. Huhtinen in
Current site
Google Scholar
PubMed
Close
 DVM, PhD

Click on author name to view affiliation information

Abstract

Objective—To determine whether sublingual detomidine gel administration to horses would be effective in providing an appropriate degree of sedation and restraint to facilitate completion of veterinary and husbandry procedures under field conditions.

Design—Multicenter, prospective, randomized, blinded, placebo-controlled clinical study.

Animals—270 client-owned horses known to require sedation or strong restraint to enable veterinary and husbandry procedures to be performed.

Procedures—Horses randomly received a single dose of detomidine gel (0.04 mg/kg [0.018 mg/lb]) or placebo gel administered sublingually. Horses were sedated to facilitate cleaning the prepuce, cutting of hair with electric clippers, hoof trimming or application of shoes, manual dental floating (ie, rasping or filing of the teeth to remove irregularities), nasogastric passage of a stomach tube or endoscope, and radiography. The primary determinant of efficacy was an assessment by a veterinarian on the ability or inability to successfully conduct the procedure.

Results—171 horses met all the study protocol criteria. One hundred twenty-nine horses were treated with detomidine. The procedure was completed successfully for 76% (98/129) of the detomidine-treated horses, while the procedure was completed successfully for only 7% (3/42) of the placebo-treated horses. The percentage of horses in which the procedure was successfully completed was significantly different between detomidine-treated horses and placebo-treated horses. No serious adverse effects were reported.

Conclusions and Clinical Relevance—Detomidine gel administered to horses sublingually at a dose of 0.04 mg/kg provided an appropriate degree of sedation and restraint to facilitate completion of veterinary and husbandry procedures in horses known to require sedation for such procedures.

Abstract

Objective—To determine whether sublingual detomidine gel administration to horses would be effective in providing an appropriate degree of sedation and restraint to facilitate completion of veterinary and husbandry procedures under field conditions.

Design—Multicenter, prospective, randomized, blinded, placebo-controlled clinical study.

Animals—270 client-owned horses known to require sedation or strong restraint to enable veterinary and husbandry procedures to be performed.

Procedures—Horses randomly received a single dose of detomidine gel (0.04 mg/kg [0.018 mg/lb]) or placebo gel administered sublingually. Horses were sedated to facilitate cleaning the prepuce, cutting of hair with electric clippers, hoof trimming or application of shoes, manual dental floating (ie, rasping or filing of the teeth to remove irregularities), nasogastric passage of a stomach tube or endoscope, and radiography. The primary determinant of efficacy was an assessment by a veterinarian on the ability or inability to successfully conduct the procedure.

Results—171 horses met all the study protocol criteria. One hundred twenty-nine horses were treated with detomidine. The procedure was completed successfully for 76% (98/129) of the detomidine-treated horses, while the procedure was completed successfully for only 7% (3/42) of the placebo-treated horses. The percentage of horses in which the procedure was successfully completed was significantly different between detomidine-treated horses and placebo-treated horses. No serious adverse effects were reported.

Conclusions and Clinical Relevance—Detomidine gel administered to horses sublingually at a dose of 0.04 mg/kg provided an appropriate degree of sedation and restraint to facilitate completion of veterinary and husbandry procedures in horses known to require sedation for such procedures.

The α2-adrenergic receptor agonists are a widely used class of sedatives in veterinary medicine. They are administered parenterally to facilitate completion of procedures in the standing horse by providing appropriate relaxation, sedation, and, when pain is present, analgesia.1–4 Detomidine has been shown to reduce stress-related hormones and metabolites in horses.5,6 Reduction in catecholamine release in detomidine-treated horses may be an indication that detomidine may have application in managing fearful responses to nonpainful procedures.

Injectable detomidine is frequently used by veterinarians under field conditions when rapid onset of sedation is desirable to facilitate completion of minor procedures of short to moderate duration in the standing horse. However, not all horses will tolerate injections. These needle-shy horses may react vigorously and can injure themselves or nearby persons. An oral route of administration is a safe and less stressful way of medicating horses. Detomidine injectable solution has been shown to produce sedation in ponies when administered sublingually.7 The degree of sedation was dose dependent and less than that produced following the same dose given IM. All signs of sedation and adverse effects observed were similar to those seen after IV administration, although ataxia and bradycardia were less pronounced after sublingual administration. Preliminary work indicates that detomidine injectable solution at label-recommended doses was ineffective when given in feed or by use of a stomach tube.a In another study,8 detomidine administered at a dose of 0.06 mg/kg (0.027 mg/lb) from a plastic syringe into the buccal space or oral cavity of horses as the injectable solution mixed with apple sauce or molasses provided a satisfactory amount of sedation. A noninjectable dosage form of detomidine would be a useful addition to the veterinary pharmacy for prescription use by qualified laypersons with horses deemed difficult to handle, and that need sedation or restraint to facilitate minor procedures.

The objective of the study presented here was to determine whether sublingual detomidine gel administration is effective in providing an appropriate degree of sedation and restraint to facilitate completion of veterinary and husbandry procedures in horses known to require sedation or strong restraint to enable similar procedures to be performed in the field.

Materials and Methods

The study was conducted in support of new drug registration and in accordance with the US FDA Center for Veterinary Medicine guideline 85: Good Clinical Practices.9

Animals—The study was conducted at private equine veterinary practices in the United States where client-owned horses were enrolled by the investigating veterinarian. Horses were eligible for enrollment if they had a satisfactory physical condition, were yearlings or older, and had a history of requiring sedation or other means of strong restraint. This information was obtained on the Data Collection Form where the investigating veterinarian had to answer yes to the question of “Does the horse have a history of requiring sedation or other means of strong restraint (eg, application of a twitch) to enable similar procedures to be performed” to qualify the horse for the study. Horse owners or their agents provided written informed consent to participate. Horses were not enrolled if they were grossly obese or emaciated; had signs of systemic disease; had a history of, or ongoing, cardiovascular abnormality; were pregnant or lactating; or had a recent history of breeding. Horses considered to be extremely fractious and too dangerous to medicate by the oral route of administration were not enrolled. Eligible procedures were use of electric clippers to cut the hair, cleaning the prepuce, trimming of hooves, application of shoes, manual rasping (floating) of teeth, radiography, or nasogastric passage of a stomach tube or endoscope. Horses were housed in their typical environments during the study, except in those instances when horses were transported to the veterinary facility where the procedure was conducted. No fasting or special dietary requirements were necessary before a horse was enrolled in the study. However, food and water were removed from the stall from the time of treatment administration until recovery from sedation.

Study design and treatment—The study was conducted as a placebo-controlled clinical trial under field conditions. Horses were randomly allocated to treatment on the basis of order of enrollment, with blocks consisting of 4 horses. Within each block, 3 horses received detomidine gelb and 1 horse received placebo. Horses in the detomidine group were treated with an oromucosal gel formulation of detomidine (7.6 mg/mL) administered once sublingually at a dose of 0.04 mg/kg (0.018 mg/lb). Placebo treatment was an oromucosal gel identical in appearance and volume to the detomidine treatment. The study drugs were supplied in unit-dose, graduated syringes (0.25-mL increments) that were numbered sequentially to match the animal number. The randomized order of treatment was incorporated into the animal number sequence so that the treatment order was not apparent to study personnel.

Experimental procedures—Body weight was determined at the time of enrollment with a chest girth weight estimation tape.10,11 A dosing table specified the horse's weight range for each 0.25-mL increment of the dose. A veterinarian, a technician, or the horse's owner or agent administered the dose. The administrator was determined by the veterinarian on the basis of the layperson's experience or willingness and the horse's demeanor.

The veterinarian evaluated the ease of gel administration (easy, manageable, or difficult), the horse's demeanor at the time of dosing (relaxed or composed, moderately agitated or excited, or markedly agitated or excited), the product acceptability (no sign of objection, accepted with mild objection but signs were momentary, or excessive objection), and whether the gel was successfully and completely administered under the tongue (yes or no). For all horses, a complete physical examination was performed prior to enrollment in the study. Approximately 15 minutes prior to treatment administration, heart rate and rhythm (regular or irregular), respiratory rate, and rectal temperature were recorded.

In addition, each horse was assigned a baseline score for sedation and ataxia. The degree of sedation was scored on a 0 to 3 scale, with 0 indicating no sedation and 3 indicating marked sedation. Ataxia was also evaluated on a 0 to 3 scale, with 0 indicating no ataxia and 3 indicating swaying and leaning with hind limbs crossed or forelimbs buckled at the carpus. These assessments were used to characterize the degree of sedation and recovery over time. After administration of detomidine or placebo, the horses were allowed to stand quietly for approximately 40 minutes to allow sedation to occur. The actual waiting period was at the discretion of the veterinarian. Heart rate and rhythm, respiratory rate, sedation, and ataxia were evaluated again 40 minutes after treatment, a time point selected through experience from previous studies.7,8,12,13

The veterinarian then completed a subjective assessment of the horse for ability to attempt the procedure on a scale of 0 to 2, with 0 indicating insufficient sedation to attempt the procedure and 2 indicating that the horse was so profoundly sedated and ataxic that the procedure could not be performed on the basis of their clinical judgment. This assessment was a safety precaution to avoid attempting a procedure on a horse that appeared to be deficiently or excessively sedated. If the degree of sedation was adequate (score = 1), the procedure was attempted. The veterinarian observed or conducted the procedure and made a subjective evaluation of the ability or inability to satisfactorily complete the procedure. The ability to complete the procedure was scored according to a scale of 0 to 3, where scores of 0 or 1 (poor or fair) were considered treatment failures and scores of 2 or 3 (good or excellent) were treatment successes (Appendix). If adequate sedation was present, additional procedures were allowed to be conducted (although only the first procedure was considered for the efficacy evaluation). After completion of the procedure, horses were allowed to stand quietly to recover from sedation. If sedation was adequate to attempt but not complete the procedure, at the veterinarian's discretion, a lip twitch could be applied or an additional sedative administered so that the procedure could be completed. When this occurred, the horse was considered a treatment failure. The degree of sedation and ataxia, if present, was observed at scheduled intervals from time of treatment administration until horses were considered recovered from sedation (sedation score, 0 or 1).

For any horse assessed 40 minutes after treatment administration that was found to be sedated, additional assessments of sedation, ataxia, heart rate and rhythm, and respiratory rate continued at 90 minutes, 120 minutes, and hourly thereafter until the horse had recovered. Rectal temperature was measured at 2 time points: prior to treatment administration and at the last time point when the horse had recovered from sedation. All horse owners or agents were interviewed 2 to 4 days after drug treatment by the veterinarian in an open-ended format either by phone or in person to determine whether the horse had any posttreatment adverse effects.

Statistical analysis—The primary efficacy variable was a binary variable derived from an assessment of the ability to attempt the procedure and an assessment of the ability or inability to complete the veterinary or husbandry procedure. This derived binary variable was analyzed with a mixed categorical model.c The model included the fixed effect of treatment. Random effects included the site, treatment by site interaction, and error. Treatment differences were assessed at the 5% level of significance (P ≤ 0.05). The null hypothesis was that the result of the primary variable analysis was independent of the treatment (placebo or detomidine gel). Secondary continuous and categorical variables were summarized. The study was powered to provide at least 80% power to detect a 25% difference between the treatments, for example success rates of 50% versus 25%. Overall incidences of reported adverse effects (ie, abnormal clinical signs that may have been expected or unexpected with use of the study product) were calculated for each treatment group.

Results

A total of 270 horses of either sex and of various ages and breeds (Table 1) were enrolled in the study at 9 equine clinics in 7 states. Two data sets of horses were summarized or statistically analyzed. Data for the 270 horses (ITT data set) that received either the study product (n = 202) or placebo (68) were summarized to assess the acceptability and potential adverse effects associated with sublingual detomidine gel administration under field conditions. Of the 270 horses enrolled, there was insufficient written historical documentation for 93 horses to support the protocol inclusion criterion specifying a history that the horse previously required sedation or strong restraint for similar procedures to be performed. An additional ± horses had major protocol deviations documented during the study that may have affected efficacy evaluation. Thus, the analysis of efficacy of detomidine gel was performed in 171 horses (PP data set). The numbers of horses distributed across the procedure types were comparable, with a slightly higher proportion of horses enrolled that underwent teeth floating (Table 2).

Table 1

Demographic characteristics of 270 horses included in the ITT data set for a study of the efficacy of sublingual administration of detomidine gel.

VariablePlacebo-treated horses (n = 68)Detomidine-treated horses (n = 202)Total horses (n = 270)
No. of horses by breed   
   Quarter Horse27 (39.7)63 (31.2)90 (33.3)
   Thoroughbred11 (16.2)51 (25.2)62 (23.0)
   Miscellaneous purebred10 (14.7)44 (21.8)54 (20.0)
   Quarter Horse crossbred6 (8.8)12 (5.9)18 (6.7)
   Thoroughbred crossbred6 (8.8)11 (5.4)17 (6.3)
   Paint3 (4.4)13 (6.4)16 (5.9)
   Miscellaneous crossbred5(7.3)8 (4.0)13 (4.8)
No. of horses by sex   
   Gelding40 (58.8)125 (61.9)165 (61.1)
   Mare24 (35.3)70 (34.7)94 (34.8)
   Stallion4 (5.9)7 (3.5)11 (4.1)
Age (y)   
   Mean ± SD8.7 ± 6.79.8 ± 6.59.5 ± 6.6
   Range1.0–36.01.5–32.01.0–36.0
Body weight (kg)*   
   Mean ± SD532 ± 54529 ± 68530 ± 65
   Range413–617268–658268–658

Values in parentheses are percentages.

To convert weight in kilograms to weight in pounds, multiply by 2.2.

Table 2

Distribution of horses by procedure type in the ITT (n = 270) and PP (171) data sets.

ProcedureNo. of horses in ITT data set (%)No. of horses in PP data set (%)
Cutting hair with electric clippers36 (13.3)32 (18.7)
Cleaning the prepuce51 (18.9)31 (18.1)
Manual rasping (floating) of teeth78 (28.9)39 (22.8)
Hoof trimming or shoe application30 (11.1)29 (17.0)
Nasogastric passage of a stomach tube or endoscope32 (11.9)15 (8.8)
Radiography43 (15.9)25 (14.6)

A period of 40 minutes (plus or minus 10 minutes) after dosing was recommended in the study protocol as an appropriate period to wait after treatment administration to allow sedation to develop. However, the actual waiting period was at the discretion of the veterinarian and varied from 20 to 147 minutes, with 90% (145/161; time not recorded for 10 horses in the PP data set) of all procedures attempted within 30 to 65 minutes after dosing.

Detomidine or placebo gel was successfully administered sublingually in 98% (264/270) of horses, and those dosed improperly received the gel in the buccal space or on the tongue. Veterinarians administered the gel 70% (189/270) of the time whereas owners and veterinary technicians administered treatments in the remaining horses (17% [46/270] and 13% [35/270] of the time, respectively). The 6 treatment administration errors occurred 4 times by veterinarians and once each by owners and technicians. Horses treated with detomidine accepted the oromucosal gel formulation with mild or no objection 99% (199/202) of the time, and horses receiving placebo gel sublingually accepted the gel 96% (65/68) of the time.

The primary determinant of efficacy was the ability to successfully complete the veterinary or husbandry procedure. In the PP data set of horses, successful procedure completion was achieved in 76% (98/129) of detomidine-treated horses and 7% (3/42) of placebo-treated horses. The difference in procedure completion between the 2 treatments was significant (P < 0.001).

Successful completion of procedures varied by the type of procedure performed (Table 3). Procedures varied in length from 1 minute (passage of nasogastric tube) to 124 minutes (shoe application or hoof trimming). Forty-two horses underwent 1 or more additional procedures while sedated for a primary procedure, including grooming, joint injections, ultrasonography, and wound cleaning and debridement.

Table 3

Number (percentage) of horses included in the PP data set (n = 171) for which there was successful completion of various procedures.

ProcedurePlacebo-treated horsesDetomidine-treated horses
Cutting hair with electric clippers0/7 (0)12/25 (48)
Cleaning the prepuce0/5 (0)21/26 (81)
Manual rasping (floating) of teeth0/12 (0)24/27 (89)
Hoof trimming or shoe application1/7 (14)19/22 (86)
Nasogastric passage of a stomach tube or endoscope0/5 (0)8/10 (80)
Radiography2/6 (33)14/19 (74)
Total3/42 (7)98/129 (76)

Forty minutes after treatment with detomidine, 54% (69/128) of horses were either moderately or markedly sedated, 41% (52/128) were minimally sedated, and 5% (7/128) were not sedated (PP data set). For 14% (18/129) of horses, moderate or marked sedation continued for up to 120 minutes, and for 1 horse, minimal sedation continued for up to 240 minutes.

Ataxia was assessed separately from sedation on a scale of 0 to 3. Of the 129 detomidine-treated horses, 19% (25/129) never demonstrated any ataxia (score = 0) and 51% (66/129) were never more than minimally ataxic (score = 1; stable but swaying slightly). Forty minutes after administration of detomidine, 27% (34/128) of horses were ataxic (score = 2; defined as swaying and leaning); at 90 minutes, this number was decreased to 9 horses; and at 180 minutes, no horses were swaying or leaning (PP data set). Only 1 detomidine-treated horse developed marked ataxia (score = 3; swaying and leaning with hind limbs crossed or fore-limbs buckled at the carpus) during the study and then only at 90 minutes after dosing.

Before treatment, mean heart rates were 43 and 43 beats/min and the mean respiratory rates were 18 and 17 breaths/min in detomidine-treated and placebo-treated groups, respectively (ITT data set). The mean heart rate and respiratory rate at approximately 40 minutes after treatment (at the onset of sedation) were 31 beats/min and 14 breaths/min, respectively, for detomidine-treated horses and 43 beats/min and 19 breaths/min, respectively, for placebo-treated horses (ITT data set). The differences in heart rate and respiratory rate between treatment groups at 40 minutes after treatment were significant (P < 0.001 and P = 0.001, respectively). Mean heart rate and mean respiratory rate continued at below pretreatment rates at other posttreatment assessment times. At 40 minutes after treatment, 21% (42/200) of detomidine-treated horses were observed to have irregular heart rhythm, compared with 1% of placebo-treated horses (ITT data set). The posttreatment assessment at 40 minutes produced the greatest incidence of observed heart rhythm irregularities. There was a small decrease (0.3°C [0.5°F]) in mean rectal temperature at the time of recovery from sedation (180 minutes) versus the pretreatment rectal temperature in detomidine-treated horses (ITT data set).

Adverse effects (ie, abnormal clinical signs observed in horses after dosing) were reported for 39 horses (66 observations) treated with detomidine and for 1 horse (1 observation) receiving placebo (ITT data set). Abnormal clinical signs included increased sweating (20 observations), penile relaxation (12 observations), irregular heart or pulse rhythm consistent with second-degree atrioventricular block (9 observations), and frequent urination (9 observations). Adverse effects with ≤ 4 observations included piloerection, facial or oral edema, hypersalivation, nasal discharge, flatulence, muscle tremors, epiphora, pale mucous membranes, and swollen sheath. All abnormal clinical signs had resolved by the time of follow-up 2 to 4 days after treatment. There were no serious adverse effects or human reactions to detomidine gel reported during the study.

Thirty-three different concomitant treatments were administered during the study either as medications for ongoing illness, prophylactic treatment, or a rescue sedative when the degree of sedation provided by the study drugs was insufficient to perform the desired procedure. The most commonly used concomitant or rescue medications were detomidine injectable solution, followed by butorphanol, glucosamine chondroitin supplements, and phenylbutazone.

Discussion

Detomidine administered as an oromucosal gel formulation provided adequate sedation and restraint needed to accomplish common veterinary or husbandry procedures in horses known to require sedation for similar procedures. When administered orally, α2-adrenergic receptor agonists are metabolized on first pass through the liver. Pharmacokinetic studies7,8,13 in horses indicate that detomidine is ineffective when administered by stomach tube and of variable efficacy when mixed with food (orally), but efficacious when given sublingually.

An inclusion criterion in the protocol was a requirement that the horse has a history of requiring sedation or other means of strong restraint to enable similar procedures to be performed. The intent was to ensure the population of study animals would provide an adequate challenge to test whether the formulation could deliver adequate sedation in horses known to require sedation.

The onset and duration of sedation observed in this study are similar to previous reports7,8 in which detomidine injectable solution was used orally. Ataxia is a common concern related to sedation. Ataxic horses can pose a risk both to themselves and to handlers, as can fractious horses that have not been sedated for veterinary and husbandry procedures. Attending veterinarians are best suited to assess the relative risks and determine a proper course of action for individual situations. The low incidence of ataxia (marked ataxia observed in 1 horse at 1 time point and moderate ataxia [swaying and leaning] observed in 7% of horses 90 minutes after dosing) indicates detomidine gel may be a treatment option in situations where stocks or other additional external restraint are not available.

The proportion of success varied by the type of procedure. Manual floating of the teeth and hoof trimming and shoeing were the most successful, whereas adequate sedation for cutting hair with electric clippers was most difficult to achieve. None of the placebo-treated horses and only half of the horses receiving detomidine gel were successfully clipped. The lower rate of success with this procedure could be attributed to reports that horses remain somewhat responsive to touch and noise following administration of α2-adrenergic receptor agonists.7 The success rate in the ability to complete other procedures ranged from 74% to 81% and 0% to 33% in horses treated with detomidine gel or placebo gel, respectively (PP data set). The success rates reported in this study are in line with the dose-finding trial conducted with this product.12 In that smaller clinical study, the ability to conduct similar procedures was successful in 11 of 12 horses that were given detomidine gel sublingually at a dose of 0.04 mg/kg, but successful in only 8 of 12 horses that were given detomidine injectable solution IM at a dose of 0.02 mg/kg (0.009 mg/lb). In the study reported here, the subjective nature of measurements was dictated by the fact that objective ways of measuring variables, such as ease of gel administration, horse's demeanor at the time of dosing, and product acceptability, do not exist. Descriptive numerical rating scales were used to quantify subjective results in each of these instances.

Decreases in heart rate and respiratory rate are expected pharmacological effects of α2-adrenergic receptor agonists. Increased incidence of irregular heart rhythm during sedation was observed (49/202 [24%] of detomidine-treated horses), although only 9 instances of irregular heart or pulse rhythm consistent with second-degree atrioventricular block were reported as adverse effects. This implies that the investigating veterinarians considered these irregularities in the heart rhythm benign and characteristic of the α2-adrenergic receptor agonist family of drugs or that the suspected second-degree atrioventricular block was not reported as an adverse effect because it is considered a common, normal variation of cardiac rhythm in the horse. Of the total number of adverse effects (n = 67) observed in 40 horses, 33 of the 40 (82.5%) horses were considered to have typical adverse effects associated with α2-adrenergic receptor agonist administration. The other adverse effects were attributable to concomitant treatment (horse developed muscle tremor after an additional injectable sedative was administered, 1/40 [2.5%]), concurrent disease (excessive flatulence, 1/40 [2.5%]), other causes (iodine scrub-related sheath dermatitis, 1/40 [2.5%]), or unspecified causes (4/40 [10%]). All adverse effects documented in the study were recorded during the study period and not in the 2-to 4-day follow-up period. Preclinical laboratory safety studies have been conducted to demonstrate the safety of this product in horses.14

Recent safe administration of detomidine injectable solution in an individual horse may indicate a decreased risk associated with the use of the oromucosal gel formulation by virtue of the experience obtained by the previous exposure. However, if the gel is prescribed for application by a layperson, the prescribing veterinarian must determine the appropriate use under a valid veterinarian-client-patient relationship. The gel is viscous and blue in color; thus, it is easy to recognize and to wash off the product should accidental exposure occur. Results of this study demonstrated the ease of correct administration of detomidine gel and its overall acceptability by horses. After a brief description of sublingual dosing, veterinarians, technicians, and horse owners or agents were all adept at administering the oromucosal gel formulation. It is assumed most doses were administered by veterinarians because of their preference to obtain substantial first-hand knowledge regarding ease of dosing, as choice of dose administrator was at the discretion of the veterinarian. Improper administration could result in oral ingestion of detomidine gel that could result in lack of sedation. The acceptability of the gel to the horse is important to ensure a complete dose can be administered with minimal resistance.

To assess product use and performance under anticipated conditions of use, certain aspects of the study were intentionally variable. It is intended that the product would be administered by a variety of people with varying skill sets. Detomidine gel is expected to be prescribed at the discretion of the treating veterinarian on the basis of the veterinarian-client-patient relationship and the specific circumstances of each situation. This study showed that the gel was able to be correctly administered in 98% of the horses by both veterinarians and laypersons. Other variations, including time between administration of drug and procedure, the type and length of procedure, and the estimation of body weight required for dosing, reproduce conditions similar to routine equine practice. However, it is recognized that further clinical studies, perhaps under more tightly controlled conditions, would have the potential to clarify the various impacts of such field variables.

Abbreviations

ITT

Intention to treat population

PP

Per protocol population

Investigating veterinarians in addition to the authors include Drs. Randy Bimes (Quakertown Veterinary Clinic, Quakertown, Pa; 42 horses), Jeff Bunn (Equine Medical LLC, Lowell, Mich; 35), Tom Daugherty (Advanced Equine Veterinary Practice, Lexington, Ky; 8), Robert Emery (Beadle Lake Veterinary Hospital, Battle Creek, Mich; 42), Amy Leibeck (Genesee Valley Equine Clinic LLC, Scottsville, NY; 17), Jason St. Romain (The Animal Center, Zachary, La; 37), and Greg Staller (Running S Equine, Califon, NJ; 10).

a.

Devitt C. Sedative action of oral detomidine: efficacy with various methods of oral administration. BVetMed dissertation, Department of Large Animal Medicine and Surgery, Royal Veterinary College, University of London, London, England, 1989.

b.

Dormosedan Gel, Orion Corp, Turku, Finland; distributed by Pfizer Animal Health, New York, NY.

c.

PROC GLIMMIX, SAS, version 9.1.3, SAS Institute Inc, Cary, NC.

References

  • 1 England GCClarke KW. Alpha 2 adrenoceptor agonists in the horse—a review. Br Vet J 1996; 152:641657

  • 2 Wagner AEMuir WW IIIHinchcliff KW. Cardiovascular effects of xylazine and detomidine in horses. Am J Vet Res 1991; 52:651657

  • 3 Moens YLanz FDoherr MG, et al. A comparison of the antinociceptive effects of xylazine, detomidine and romifidine on experimental pain in horses. Vet Anaesth Analg 2003; 30:183190

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 4 Lemke KA. Anticholinergics and sedatives. In: Tranquilli WJThurmon JCGrimm KA, eds. Lumb & Jones' veterinary anesthesia and analgesia. 4th ed. Ames, Iowa: Wiley-Blackwell, 2007;203240.

    • Search Google Scholar
    • Export Citation
  • 5 Raekallio MVainio OScheinin M. Detomidine reduces the plasma catecholamine, but not cortisol concentrations in horses. Zentralbl Veterinarmed A 1991; 38:153156

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 6 Carroll GLMatthews NSHartsfield SM, et al. The effect of detomidine and its antagonism with tolazoline on stress-related hormones, metabolites, physiologic responses, and behavior in awake ponies. Vet Surg 1997; 26:6977

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 7 Malone JHClarke KW. A comparison of the efficacy of detomidine by sublingual and intramuscular administration in ponies. Vet Anaesth Analg 1993; 20:7377

    • Search Google Scholar
    • Export Citation
  • 8 Ramsay ECGeiser DCarter W, et al. Serum concentrations and effects of detomidine delivered orally to horses in three different mediums. Vet Anaesth Analg 2002; 29:219222

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 9 FDA Center for Veterinary Medicine. Guidance for Industry No. 85: good clinical practice. VICH GL9. Available at: www.fda.gov/downloads/AnimalVeterinary/GuidanceComplianceEnforcement/GuidanceforIndustry/ucm052417.pdf. Accessed Dec 4, 2009.

    • Crossref
    • Export Citation
  • 10 Carroll CLHuntington PJ. Body condition scoring and weight estimation of horses. Equine Vet J 1988; 20:4145

  • 11 Asquith RLJohnson ELKivipelto J, et al. Erroneous weight estimation of horses, in Proceedings. 36th Annu Conv Am Assoc Equine Pract 1991;599607.

    • Search Google Scholar
    • Export Citation
  • 12 Kaukinen HAspegrén JHuhtinen M. Sedative effects of detomidine after intramuscular injection and sublingual administration of oromucosal gel to horses. Vet Anaesth Analg 2009; 36:9.

    • Search Google Scholar
    • Export Citation
  • 13 Kaukinen HAspegrén JHyyppä S, et al. Bioavailability of detomidine administered to horses as an oromucosal gel and comparison of sedative effects after three administration routes. [published online ahead of print Jul 8, 2010] J Vet Pharmacol Ther doi: 10.1111/j.1365–2885.2010.01193.x.

    • Search Google Scholar
    • Export Citation
  • 14 Freedom of Information Summary, Dormosedan Gel, NADA 141–306 March 22, 2010.

    • Crossref
    • Export Citation

Appendix

Scoring system used to describe the ability to complete a procedure in sedated horses.

ScoreCategoryDescription
0PoorStrong resistance; a lip twitch was required and the procedure was only completed with difficulty or could not be completed.
  OR
  The horse became too sedated or ataxic such that the procedure could not be completed.
  OR
  The procedure was not attempted because of absent, poor, or excessive sedation.
1FairModerate resistance observed such that the procedure could not be performed without the aid of a lip twitch.
2GoodSome resistance, but the procedure could be performed.
3ExcellentProcedure could be easily performed without substantial resistance.
All Time Past Year Past 30 Days
Abstract Views 145 0 0
Full Text Views 871 803 189
PDF Downloads 192 117 12
Advertisement