Detomidine Gel Research Articles

Sedative effects and pharmacokinetics of detomidine when administered intravenously and intravaginally as a gel to alpacas

Introduction: The objectives of the study were to evaluate the sedative effects and pharmacokinetics of detomidine gel when administered intravaginally (IVG) to alpacas, and to compare the results with intravenously (IV) administered detomidine hydrochloride.

Use of Detomidine Oromucosal Gel for Alleviation of Acute Anxiety and Fear in Horses: A Pilot Study.

The aim of this randomized, double-blind, placebo-controlled, parallel group clinical field study was to evaluate the effect of detomidine oromucosal gel in alleviating anxiety and fear in horses. Sixteen horses with a history of acute anxiety and fear associated with firework-related noise entered the study. On New Year's Eve, eight horses were treated with 30 μg/kg detomidine gel and eight horses with placebo gel. When fireworks were present, 75% (6/8) of the detomidine-treated horses were scored by their owners as having a good or excellent treatment effect on anxiety and fear, while 50% (3/6) of horses receiving placebo were scored to have a good effect. Horses' behavior was video-recorded and assessed with a focal animal continuous method by a treatment-blind expert observer. Results showed that when fireworks were present, walking behavior decreased significantly (p < 0.05) after treatment with detomidine and that horses of the placebo group, overall, showed more restlessness, vocalization, and signs of colic (Wilcoxon matched-pairs test on the first PC, p = 0.007). This study indicates that detomidine oromucosal gel can be used to alleviate acute noise-related anxiety and fear in horses, but larger treatment groups are needed to confirm the results.

Sedative effects and pharmacokinetics of detomidine when administered intravenously and intravaginally as a gel in alpacas

ObjectivesTo evaluate the sedative effects and pharmacokinetics of detomidine gel administered intravaginally to alpacas in comparison with intravenously (IV) administered detomidine. Study designRandomized, crossover, blinded experiment. AnimalsA group of six healthy adult female Huacaya alpacas (70.3 ± 7.9 kg). MethodsAlpacas were studied on two occasions separated by ≥5 days. Treatments were IV detomidine hydrochloride (70 μg kg−1; treatment DET–IV) or detomidine gel (200 μg kg−1; treatment DET–VAG) administered intravaginally. Sedation and heart rate (HR) were evaluated at intervals for 240 minutes. Venous blood was collected at intervals for 360 minutes after treatment for analysis of detomidine, carboxydetomidine and hydroxydetomidine using liquid chromatography–tandem mass spectrometry. Measured variables were compared between treatments and over time using mixed model analysis. Data are presented as the mean ± standard error of the mean, and a p value of <0.05 was considered significant. ResultsOnset of sedation was faster in treatment DET–IV (1.6 ± 0.2 minutes) than in treatment DET–VAG (13.0 ± 2.5 minutes). Time to maximum sedation was shorter in treatment DET–IV (8.3 ± 1.3 minutes) than in treatment DET–VAG (25 ± 4 minutes). Duration of sedation was not different between treatments. There was a significant linear relationship between sedation score and plasma detomidine concentration. HR was less than baseline for 60 and 125 minutes for treatments DET–IV and DET–VAG, respectively. The maximal decrease in HR occurred at 15 minutes for both treatments. The mean maximum plasma concentration of detomidine, time to maximum concentration and bioavailability for treatment DET–VAG were 39.6 ng mL−1, 19.9 minutes and 20%, respectively. Conclusions and clinical relevanceDetomidine administration at the doses studied resulted in moderate sedation when administered IV or intravaginally to alpacas.

Pharmacokinetics, sedation and hemodynamic changes following the administration of oral transmucosal detomidine gel in cats.

The aim of this study was to describe the pharmacokinetics of oral transmucosal (OTM) detomidine gel in healthy cats and assess its effects on sedation and hemodynamic variables. Eight adult cats weighing 4.12 kg ± 0.72 received 4 mg/m2 detomidine gel onto the buccal mucosa. Level of sedation, heart rate (HR), blood pressure (BP) and respiratory rate (f R) were assessed at predetermined intervals following administration. Blood samples for plasma detomidine concentrations and venous blood gas variables were collected from a medial saphenous catheter. Plasma detomidine concentrations were analyzed using ultra-high-pressure liquid chromatography with mass spectrometry detection, and pharmacokinetic estimates were obtained with compartmental methods. Data were analyzed using ANOVA and paired t-test or appropriate non-parametric tests. Sedation occurred in all cats, and was increased from baseline at 30 mins (P <0.001). Decreases in HR occurred from 15-60 mins, ranging from 140 to 165 beats per min (P <0.001). Blood glucose increased from 101 ± 12 mg/dl to 168 ± 27.3 mg/dl at 60 mins (P = 0.004). Systolic blood pressure decreased from baseline (139 ± 14.8 mmHg) to 103 ± 23.0 mmHg at 60 mins (P = 0.023). All changes abated by 120 mins. Emesis occurred in 7/7 cats within 2 mins of gel administration. Geometric mean (coefficient of variation) for clearance was 220.7 ml/min/kg (35.3 ml/min/kg), volume of distribution was 14.9 l/kg (39.9 l/kg) (both a function of bioavailability) and elimination half-life was 46.9 mins (16.0 mins). Maximum plasma concentrations of 10.5 ng/ml (35.5 ng/ml) detomidine occurred at 36.9 mins (21.5 mins). OTM detomidine gel produced moderate sedation with minimal undesirable side effects in healthy cats, although emesis occurred in all cats. The pharmacokinetic profile supports short-term, minimally invasive sedation in this species. Further studies are warranted to assess its safety and feasibility for use in debilitated cats, or prior to general anesthesia.

Evaluation of the sedative effects and pharmacokinetics of detomidine gel administered intravaginally to horses

ObjectivesTo determine the sedative effects and pharmacokinetic profile of detomidine when administered intravaginally as a gel formulation to horses. Study designRandomized, crossover, masked experimental design. AnimalsA group of six healthy adult mares (494 ± 56 kg). MethodsMares were studied on two occasions and were administered either detomidine hydrochloride (10 μg kg–1) intravenously (treatment IV) or detomidine gel (40 μg kg–1) intravaginally (treatment IVG), separated by 1 week. Sedation, ataxia, muzzle–floor distance and heart rate (HR) were evaluated every 15 minutes for 240 minutes. Venous blood samples were collected at 15, 30, 45, 60, 90, 120, 150, 180, 240, 300 and 360 minutes postadministration and were analyzed for detomidine and metabolites using liquid chromatography–tandem mass spectrometry. Measured variables were compared over time and between treatments using mixed model analysis. Correlation between drug plasma concentrations and muzzle–floor distance, and sedation and ataxia scores was determined using the Spearman correlation coefficient. Data are presented as mean ± standard error of the mean and p value was set at <0.05. ResultsSedation was shorter with IV (119 ± 16 minutes) than with IVG (188 ± 22 minutes). Ataxia scores remained greater than baseline for 90 and 135 minutes for treatments IV and IVG, respectively. HR was lower than baseline for 45 and 30 minutes for IV and IVG, respectively, but did not differ between treatments. The mean maximum plasma concentration of detomidine, time to maximum concentration and bioavailability for treatment IVG was 8.57 ng mL–1, 0.37 hour and 25%, respectively. There was a significant correlation (r = 0.68) between plasma detomidine concentrations and sedation score. Conclusions and clinical relevanceDetomidine gel administered intravaginally resulted in clinically important sedation and is a viable method for detomidine gel delivery in mares.

Pharmacokinetics and sedative effects of detomidine gel administered intravaginally in horses

Introduction: The objectives of this study were to determine the sedative effects and pharmacokinetics of detomidine gel administered intravaginally in horses.

Pharmacokinetics, sedation, and hemodynamic changes following administration of oral transmucosal detomidine gel in cats

Pharmacokinetics, sedation, and hemodynamic changes following administration of oral transmucosal detomidine gel in cats

Sedation and mechanical hypoalgesia after sublingual administration of detomidine hydrochloride gel to donkeys

OBJECTIVE To compare sedative and mechanical hypoalgesic effects of sublingual administration of 2 doses of detomidine gel to donkeys. DESIGN Randomized blinded controlled trial. ANIMALS 6 healthy castrated male donkeys. PROCEDURES In a crossover study design, donkeys received each of the following sublingual treatments 1 week apart in a randomly assigned order: 1 mL of molasses (D0) or detomidine hydrochloride gel at 20 μg/kg (9 μg/lb; D20) or 40 μg/kg (18 μg/lb; D40). Sedation score (SS), head height above the ground (HHAG), and mechanical nociceptive threshold (MNT) were assessed before and for 180 minutes after treatment. Areas under the effect change-versus-time curves (AUCs) from 0 to 30, 30 to 60, 60 to 120, and 120 to 180 minutes after administration were computed for SS, HHAG, and MNT and compared among treatments. RESULTS D20 and D40 resulted in greater SS AUCs from 60 to 120 minutes and smaller HHAG AUCs from 30 through 180 minutes than did D0. The D40 resulted in smaller HHAG AUCs from 60 to 120 minutes than did D20. Compared with D0 values, MNT AUCs from 60 to 120 minutes were higher for D20, whereas MNT AUCs from 30 through 180 minutes were higher for D40. CONCLUSIONS AND CLINICAL RELEVANCE D20 and D40 induced sedation and mechanical hypoalgesia in donkeys by > 30 minutes after administration, but only sedation was dose dependent. Sublingual administration of detomidine gel at 40 μg/kg may be useful for sedation of standing donkeys prior to potentially painful minor procedures.

Pharmacokinetics of detomidine following intravenous or oral-transmucosal administration and sedative effects of the oral-transmucosal treatment in dogs.

To determine the pharmacokinetics of detomidine hydrochloride administered IV (as an injectable formulation) or by the oral-transmucosal (OTM) route (as a gel) and assess sedative effects of the OTM treatment in healthy dogs. 12 healthy adult dogs. In phase 1, detomidine was administered by IV (0.5 mg/m(2)) or OTM (1 mg/m(2)) routes to 6 dogs. After a 24-hour washout period, each dog received the alternate treatment. Blood samples were collected for quantification via liquid chromatography with mass spectrometry and pharmacokinetic analysis. In phase 2, 6 dogs received dexmedetomidine IV (0.125 mg/m(2)) or detomidine gel by OTM administration (0.5 mg/m(2)), and sedation was measured by a blinded observer using 2 standardized sedation scales while dogs underwent jugular catheter placement. After a l-week washout period, each dog received the alternate treatment. Median maximum concentration, time to maximum concentration, and bioavailability for detomidine gel following OTM administration were 7.03 ng/mL, 1.00 hour, and 34.52%, respectively; harmonic mean elimination half-life was 0.63 hours. All dogs were sedated and became laterally recumbent with phase 1 treatments. In phase 2, median global sedation score following OTM administration of detomidine gel was significantly lower (indicating a lesser degree of sedation) than that following IV dexmedetomidine treatment; however, total sedation score during jugular vein catheterization did not differ between treatments. The gel was subjectively easy to administer, and systemic absorption was sufficient for sedation. Detomidine gel administered by the OTM route provided sedation suitable for a short, minimally invasive procedure in healthy dogs.

Oral Transmucosal Detomidine Gel for the Sedation of the Domestic Ferret (Mustela putorius furo)

The restraint of ferrets for physical examination and venipuncture often employs chemical means with parenteral drug injection or inhalant anesthetics. These methods often result in agitation, pain at the injection site, increased stress, and increased cost. A transmucosal (TM) detomidine gel has recently been evaluated for sedation to facilitate physical examination and common procedures in dogs and horses. The purpose of the present study was to evaluate TM detomidine in the domestic ferret for physical examination and venipuncture in a teaching laboratory setting. Detomidine was evaluated at 2 doses: 2 and 4mg/m2. A total of 16 ferrets (8 female and 8 male) were randomly assigned to each dose group. Following the administration of detomidine, physiologic variables were collected (heart rate, respiratory rate, and rectal temperature) and sedation scoring was performed every 10 minutes. Owing to the rapid effect of the drug, time of onset was not consistently captured in the data recording protocol; the 8 males were used again in a subsequent laboratory and dosed at 3mg/m2 to refine the times of initial effect and dorsal recumbency. Venipuncture was attempted only after full physical examinations were completed and the ferrets could be placed in dorsal recumbency. Venipuncture was performed with detomidine sedation alone on 4 female and 5 male ferrets, with no significant difference based on dose group. Isoflurane was administered via face mask to the remaining ferrets due to insufficient sedation based on muscle movement and reaction to venipuncture. Heart rate significantly decreased following detomidine administration as compared with baseline values in both dose groups. There were no significant changes in respiratory rates. Sedation scores were significantly increased throughout the study period. Side effects of detomidine administration included piloerection of the tail in all ferrets and a second-degree atrioventricular block in one female ferret that resolved following reversal with atipamezole. Hyperglycemia was observed in 67% of the ferrets. TM detomidine effectively sedated domestic ferrets for physical examination and venipuncture.

An accelerometric measure of the gait pattern in horses after the administration of sublingual detomidine

The locomotor pattern alterations produced after the administration of a sublingual detomidine gel was measured by an accelerometric method in horses. Using a randomized two-way crossover design, all animals (n = 6) randomly received either detomidine gel or a placebo administered sublingually. A triaxial accelerometric device was used for gait assessment 15 minutes before (baseline) and every 10 minutes after each treatment for a period of 180 minutes. Eight different parameters were calculated, including speed, stride frequency, stride length, regularity, dorsoventral, propulsion, mediolateral, and total power. Force of acceleration and the three components of power were also calculated. Significant statistical differences were observed between groups in all the parameters but stride length. The majority of significant changes started between 30 and 70 minutes after drug administration and lasted for 160 minutes. This route of administration is definitely useful in horses in which a prolonged sedation is required, with stability being a major concern.

Sublingual administration of detomidine to calves prior to disbudding: a comparison with the intravenous route

ObjectiveTo study the effects of oromucosal detomidine gel administered sublingually to calves prior to disbudding, and to compare its efficacy with intravenously (IV) administered detomidine. Study designRandomised, prospective clinical study. AnimalsTwenty dairy calves aged 12.4 ± 4.4days (mean ± SD), weight 50.5 ± 9.0 kg. MethodsDetomidine at 80 μg kg−1 was administered to ten calves sublingually (GEL) and at 30 μg kg−1 to ten control calves IV (V. jugularis). Meloxicam (0.5 mg kg−1) and local anaesthetic (lidocaine 3 mg kg−1) were administered before heat cauterization of horn buds. Heart rate (HR), body temperature and clinical sedation were monitored over 240 minutes. Blood was collected from the V. cephalica during the same period for drug concentration analysis. Pharmacokinetic variables were calculated from the plasma detomidine concentration-time data using non-compartmental methods. Statistical analyses compared routes of administration by Student’s t-test and linear mixed models as relevant. ResultsThe maximum plasma detomidine concentration after GEL was 2.1 ± 1.2 ng mL−1 (mean ±SD) and the time of maximum concentration was 66.0 ± 36.9 minutes. The bioavailability of detomidine was approximately 34% with GEL. Similar sedation scores were reached in both groups after administration of detomidine, but maximal sedation was reached earlier in the IV group (10 minutes) than in the GEL group (40 minutes). HR was lower after IV than GEL from 5 to 10 minutes after administration. All animals were adequately sedated, and we were able to administer local anaesthetic without resistance to all of the calves before disbudding. Conclusions and clinical relevanceOromucosally administered detomidine is an effective sedative agent for calves prior to disbudding.

The use of oral transmucosal detomidine hydrochloride gel to facilitate handling in dogs

Safe and humane handling in the veterinary clinic can be challenging when dealing with fearful or anxious dogs. Historically, alpha-2 adrenergic agonists have been used via parenteral routes to facilitate handling of difficult canine subjects. Detomidine hydrochloride is an alpha-2 agonist sedative commercially available in an oral transmucosal (OTM) formulation (Dormosedan Gel; Pfizer Animal Health, Madison, NJ) approved for sedation and restraint in horses. The usefulness of this detomidine formulation has not been previously reported in dogs. This study evaluated the behavioral and physiological effects of OTM detomidine gel administration in dogs to assess its efficacy and safety for facilitation of handling canine subjects. Six healthy institution-owned adult dogs were administered detomidine gel at a dose of 0.35 mg/m2 via OTM route. Behavioral and physiological assessments were performed pretreatment and repeated every 15–30 minutes for 5 hours after administration. Behavioral assessments included global sedation (GS), composite sedation (CS), global anxiolysis (GA), and ease of handling (EH) scores. Physiological assessments included heart rate and rhythm, respiratory rate, mucous membrane color, indirect blood pressure, rectal temperature, oxygen saturation, and capillary refill time. Posttreatment GS, CS, GA, and EH scores were improved for all 6 subjects as compared with pretreatment. For 4 of 6 dogs, maximal GS scores occurred at 45 minutes posttreatment, and duration of maximal GS scores was 30 minutes. Five of 6 dogs achieved adequate GS scores. EH scores were significantly higher during time points of adequate GS scores as compared with time points when adequate GS scores were not achieved. The physiological measures revealed transient bradycardia in 5 of 6 dogs and intermittent second-degree atrioventricular block in 1 dog. No other significant adverse events were noted, and all dogs recovered uneventfully. OTM detomidine gel was safely administered to 6 dogs at a dose of 0.35 mg/m2 and resulted in measurable sedation, anxiolysis, and improved EH in all subjects. Although further evaluation is warranted for use in client-owned dogs, OTM detomidine gel offers a novel sedative and anxiolytic option to facilitate handling of canine subjects.

Sublingual administration of detomidine in horses: Sedative effect, analgesia and detection time

A single dose of 40μg/kg bodyweight (BW) of oromucosal detomidine gel was administered sublingually to 10 healthy Dutch Warmblood mares aged 7±4years (mean±SD) and BW 580±69kg. Blood and urine samples were collected before and for 8days following administration and evaluated qualitatively in an FEI Reference Laboratory and quantitatively in a research laboratory. Clinical effects were evaluated at baseline and for 24h after administration. Sedation was determined using head height and scores of reaction to auditory and mixed auditory/sensory stimuli. Mechanical nociceptive thresholds (MNTs) were assessed using pressure algometry to evaluate analgesia. Heart rate (HR) was measured and ataxia scored.All horses were considered negative for detomidine in blood samples by 48h post-administration and in urine by 60h. These results indicated that a safe withdrawal time for detomidine oromucosal gel may be 72h following a single sublingual administration of 40μg/kgBW. Decreases in HR and head height were maximal at 40 and 60min post-administration, respectively. The maximal decrease in response to stimuli was observed at 100min. Ataxia was maximal at 60min. At 40 and 80min MNTs were significantly increased compared to baseline. All parameters, except the MNTs of two locations, which were decreased, returned to baseline values within 24h post-administration.

Pharmacokinetics and pharmacodynamics of detomidine following sublingual administration to horses

To characterize pharmacokinetics and pharmacodynamics of detomidine gel administered sublingually in accordance with label instructions to establish appropriate withdrawal guidelines for horses before competition. 12 adult racehorses. 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. 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. 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.

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

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. Multicenter, prospective, randomized, blinded, placebo-controlled clinical study. 270 client-owned horses known to require sedation or strong restraint to enable veterinary and husbandry procedures to be performed. 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. 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. 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.