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.     

A comparison of the efficacy of detornidine by sublingual and intramuscular administration in ponies

Preliminary trials established that, whilst detomidine is ineffective if given by stomach tube and is of variable efficacy in food, it can give effective sedation when administered by the sublingual route. A comparison was made in four ponies of the behavioural effects, and the effects on heart rate of detomidine at three dose rates (20, 40 and 80 μg/kg) given either by intramuscular injection or sublingually by squirting the drug under the tongue. Sedation was assessed by measuring the lowering of the ponies' heads and by scoring their responses to a variety of imposed stimuli. Ponies became sedated following detomidine administration at all doses and by all routes. The lowering of the head induced by detomidine was significantly influenced by the dose of drug and by the route of administration. For either route, higher doses produced the greatest effect. There was a significant correlation between the effects produced by the two routes of administration, the lowering of the head following sublingual administration being approximately threequarters of that after the same dose given intramuscularly. Onset of sedation was achieved more rapidly following intramuscular dosing than after sublingual administration. Falls in heart rate were similar after all drug administrations, but bradycardia was never profound. Subsequent clinical experience has proved that, providing adequate time (45 minutes) is allowed for maximal effects, sublingual administration of detomidine (40 μg/kg) can give a useful degree of sedation in horses which are difficult to inject.     

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.     

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.     

Effect of yohimbine on detomidine induced changes in behavior,cardiac and blood parameters in the horse

ObjectiveTo describe selected pharmacodynamic effects of detomidine and yohimbine when administered alone and in sequence.Study designRandomized crossover design.AnimalsNine healthy adult horses aged 9 ± 4 years and weighing 561 ± 56 kg.MethodsThree dose regimens were employed in the current study. 1) 0.03 mg kg^?1 detomidine IV, 2) 0.2 mg kg^?1 yohimbine IV and 3) 0.03 mg kg^?1 detomidine IV followed 15 minutes later by 0.2 mg kg^?1 yohimbine IV. Each horse received all three treatments with a minimum of 1 week between treatments. Blood samples were obtained and plasma analyzed for detomidine and yohimbine concentrations by liquid chromatography-mass spectrometry. Behavioral effects, heart rate and rhythm, glucose, packed cell volume and plasma proteins were monitored.ResultsYohimbine rapidly reversed the sedative effects of detomidine in the horse. Additionally, yohimbine effectively returned heart rate and the percent of atrio-ventricular conduction disturbances to pre-detomidine values when administered 15 minutes post-detomidine administration. Plasma glucose was significantly increased following detomidine administration. The detomidine induced hyperglycemia was effectively reduced by yohimbine administration. Effects on packed cell volume and plasma proteins were variable.Conclusions and clinical relevanceIntravenous administration of yohimbine effectively reversed detomidine induced sedation, bradycardia, atrio-ventricular heart block and hyperglycemia.     

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.     

Serum concentrations and effects of detomidine delivered orally to horses in three different mediums

Objective To compare the effect of orally delivered detomidine on head posture when administered alone or in combination with two different food items, and to determine the serum concentrations of detomidine after oral delivery. Study Design Prospective randomized experimental study. Animals Fifteen adult grade mares weighing 328–537 kg. Methods The horses were randomly assigned to one of the three treatment groups (five horses each). The groups were given detomidine (0.06 mg kg^?1): alone; mixed with 3 mL of an apple sauce and gum mixture; or mixed with 3 mL molasses. Head droop, measured before treatment and at 15, 30, 45, 60, 75, 90, and 105 minutes after treatment, was used to evaluate sedation. Yohimbine (0.1 mg kg^?1 IV) was administered after the 90‐minute evaluation. Blood samples were collected from the detomidine‐alone group before treatment and at 15, 30, 45, 60, 75, and 90 minutes after treatment. Sera were analyzed for detomidine equivalent concentrations by an ELISA. Head droop percentages were compared using a repeated measures analysis of variance. Results Significant mean head droop developed in each treatment group by 30 minutes and persisted until reversal with yohimbine. After yohimbine administration, head positions returned to 87–91% of pre‐treatment levels. There were no significant differences among the oral treatment groups at any time. Mean serum detomidine equivalents increased slowly until 45‐minute post‐administration, but never exceeded 30 ng mL^?1. Conclusions Orally administered detomidine results in measurable serum drug concentrations using any of the delivery mediums investigated, and can be expected to produce profound head droop in horses approximately 45 minutes after administration.     

Pharmacokinetics of detomidine administered to horses at rest and after maximal exercise

Reason for performing study: Increased doses of detomidine are required to produce sedation in horses after maximal exercise compared to calm or resting horses. Objectives: To determine if the pharmacokinetics of detomidine in Thoroughbred horses are different when the drug is given during recuperation from a brief period of maximal exercise compared to administration at rest. Methods: Six Thoroughbred horses were preconditioned by exercising them on a treadmill. Each horse ran a simulated race at a treadmill speed that caused it to exercise at 120% of its maximal oxygen consumption. One minute after the end of exercise, horses were treated with detomidine. Each horse was treated with the same dose of detomidine on a second occasion a minimum of 14 days later while standing in a stocks. Samples of heparinised blood were obtained at various time points on both occasions. Plasma detomidine concentrations were determined by liquid chromatographymass spectrometry. The plasma concentration vs. time data were analysed by nonlinear regression analysis. Results: Median back‐extrapolated time zero plasma concentration was significantly lower and median plasma half‐life and median mean residence time were significantly longer when detomidine was administered after exercise compared to administration at rest. Median volume of distribution was significantly higher after exercise but median plasma clearance was not different between the 2 administrations. Conclusions and potential relevance: Detomidine i.v. is more widely distributed when administered to horses immediately after exercise compared to administration at rest resulting in lower peak plasma concentrations and a slower rate of elimination. The dose requirement to produce an equivalent effect may be higher in horses after exercise than in resting horses and less frequent subsequent doses may be required to produce a sustained effect.     

Cardiorespiratory and metabolic effects of xylazine, detomidine, and a combination of xylazine and acepromazine administered after exercise in horses

OBJECTIVE: To determine sedative, cardiorespiratory and metabolic effects of xylazine hydrochloride, detomidine hydrochloride, and a combination of xylazine and acepromazine administered i.v. at twice the standard doses in Thoroughbred horses recuperating from a brief period of maximal exercise. ANIMALS: 6 adult Thoroughbreds. PROCEDURE: Horses were preconditioned by exercising them on a treadmill to establish a uniform level of fitness. Each horse ran 4 simulated races, with a minimum of 14 days between races. Simulated races were run at a treadmill speed that caused horses to exercise at 120% of their maximal oxygen consumption. Horses ran until they were fatigued or for a maximum of 2 minutes. One minute after the end of exercise, horses were treated i.v. with xylazine (2.2 mg/kg of body weight), detomidine (0.04 mg/kg), a combination of xylazine (2.2 mg/kg) and acepromazine (0.04 mg/kg), or saline (0.9% NaCl) solution. Treatments were randomized so that each horse received each treatment once, in random order. Cardiopulmonary indices were measured, and samples of arterial and venous blood were collected immediately before and at specific times for 90 minutes after the end of each race. RESULTS: All sedatives produced effective sedation. The cardiopulmonary depression that was induced was qualitatively similar to that induced by administration of these sedatives to resting horses and was not severe. Sedative administration after exercise prolonged the exercise-induced increase in body temperature. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of xylazine, detomidine, or a combination of xylazine-acepromazine at twice the standard doses produced safe and effective sedation in horses that had just undergone a brief, intense bout of exercise.     

The influence of atipamezole on the cardiovascular effects of detomidine in horses

The reversal of the cardiovascular effects of the α₂-adrenoceptor agonist detomidine by the α₂-antagonist atipamezole was studied. Nine horses were given detomidine 20 μg/kg iv. On a separate occasion they were given atipamezole 100 μg/kg iv 15 mins after the detomidine injection. Blood gas tensions were measured and clinical signs of sedation were also observed. Bradycardia and the frequency of heart blocks induced by detomidine were reduced after atipamezole and blood pressure decreased. These reversal effects of atipamezole were of short duration (a few minutes) at the dose level tested. Two of the nine horses exhibited premature depolarisations after administration of detomidine, but not after atipamezole injection. PaO₂ decreased and PaCO₂ increased slightly after detomidine injection, but the arterial pH was within reference values or slightly elevated. Administration of atipamezole did not alter these values. Base excess rose after detomidine, and it decreased more quickly towards the baseline level, when the horses were given detomidine alone. No clinical adverse effects were seen from the administration of atipamezole. Atipamezole may be beneficial, if detomidine-induced bradycardia needs to be reversed in horses.     

Preliminary study of the effects of xylazine or detomidine with or without butorphanol for standing sedation in dairy cattle

The sedative effect induced by administering xylazine hydrochloride or detomidine hydrochloride with or without butorphanol tartrate to standing dairy cattle was compared in two groups of six adult, healthy Holstein cows. One group received xylazine (0.02 mg/kg i.v.) followed by xylazine (0.02 mg/kg) and butorphanol (0.05 mg/kg i.v.) 1 week later. Cows in Group B received detomidine (0.01 mg/kg i.v.) followed by detomidine (0.01 mg/kg i.v.) and butorphanol (0.05 mg/kg i.v.) 1 week later. Heart rate, respiratory rate, and arterial blood pressure were monitored and recorded before drugs were administered and every 10 minutes for 1 hour after drug administration. The degree of sedation was evaluated and graded. Cows in each treatment group had significant decreases in heart rate and respiratory rate after test drugs were given. Durations of sedation were 49.0 +/- 12.7 minutes (xylazine), 36.0 +/- 14.1 (xylazine with butorphanol), 47.0 +/- 8.1 minutes (detomidine), and 43.0 +/- 14.0 minutes (detomidine with butorphanol). Ptosis and salivation were observed in cows of all groups following drug administration. Slow horizontal nystagmus was observed from three cows following administration of detomidine and butorphanol. All cows remained standing while sedated. The degree of sedation seemed to be most profound in cows receiving detomidine and least profound in cows receiving xylazine.     

Hormonal, metabolic and physiological effects of laparoscopic surgery using a detomidine-buprenorphine combination in standing horses

Objective To assess the hormonal, metabolic and physiological effects of laparascopic surgery performed under a sedative analgesic combination of detomidine and buprenorphine in standing horses. Study design Prospective study. Animals Eight healthy adult Dutch Warmblood horses and five healthy adult ponies undergoing laparoscopy were studied. Five healthy adult horses not undergoing laparoscopy were used as a control group. Methods The sedative effect of an initial detomidine and buprenorphine injection was maintained using a continuous infusion of detomidine alone. The heart and respiratory rate, arterial blood pH and arterial oxygen and carbon dioxide tensions were monitored, while blood samples were taken for the measurement of glucose, lactate, cortisol, insulin and nonesterified fatty acids (NEFA). The same variables were monitored in a control group of horses which were sedated, but which did not undergo surgery. At the end of the sedation period the effects of detomidine were antagonized using atipamezole. Results The protocol provided suitable conditions for standing laparoscopy in horses. Laparoscopy induced obvious metabolic and endocrine responses which, with the exception of NEFA values, were not significantly different from changes found in the control group. While atipamezole did not produce detectable adverse effects, it is possible that anatagonism may not be essential. Conclusions The technique described reliably produces adequate sedation and analgesia for laparoscopic procedures. The level of sedation/analgesia was controlled by decreasing or increasing the infusion rate. Antagonism of the effects of detomidine may not be necessary in all cases.     

Qualitative and quantitative characteristics of the electroencephalogram in normal horses after sedation

Background

The administration of certain sedatives has been shown to promote sleep in humans. Related agents induce sleep‐like behavior when administered to horses. Interpretation of electroencephalograms (EEGs) obtained from sedated horses should take into account background activity, presence of sleep‐related EEG events, and the animal's behavior.

Hypothesis

Sedatives induce states of vigilance that are indistinguishable on EEGs from those that occur naturally.

Animals

Six healthy horses.

Methods

Digital EEG with video was recorded after administration of 1 of 4 sedatives (acepromazine, butorphanol, xylazine, or detomidine). Serum drug concentrations were measured. Recordings were reviewed, states were identified, and representative EEG samples were analysed. These data were compared with data previously obtained during a study of natural sleep.

Results

Butorphanol was associated with brief episodes resembling slow wave sleep in 1 horse. Acepromazine led to SWS in 3 horses, including 1 that also exhibited rapid eye movement sleep. Periods of SWS were observed in all horses afer xylazine or detomidine administration. Normal sleep‐related EEG events and heart block, occurred in association with SWS regardless of which sedative was used. Spectral data varied primarily by state, but some differences were observed between sedative and natural data.

Conclusions and Clinical Importance

Qualitatively, EEG findings appeared identical whether sedation‐induced or naturally occurring. The startle response and heart block associated with some sedatives may be related to sleep. Alpha₂ agonists can be used to obtain high quality EEGs in horses, but acepromazine does not promote a relaxed state in all animals.     

The effects of detomidine, romifidine or acepromazine on echocardiographic measurements and cardiac function in normal horses

OBJECTIVE: To evaluate by echo- and electrocardiography the cardiac effects of sedation with detomidine hydrochloride, romifidine hydrochloride or acepromazine maleate in horses. STUDY DESIGN: An experimental study using a cross-over design without randomization. ANIMALS: Eight clinically normal Standardbred trotters. MATERIALS AND METHODS: Echocardiographic examinations (two-dimensional, guided M-mode and colour Doppler) were recorded on five different days. Heart rate (HR) and standard limb lead electrocardiograms were also obtained. Subsequently, horses were sedated with detomidine (0.01 mg kg(-1)), romifidine (0.04 mg kg(-1)) or acepromazine (0.1 mg kg(-1)) administered intravenously and all examinations repeated. RESULTS: Heart rate before treatment with the three drugs did not differ significantly (p = 0.98). Both detomidine and romifidine induced a significant decrease (p < 0.001) in HR during the first 25 minutes after sedation; while acepromazine had a varying effect on HR. For detomidine, there was a significant increase in LVIDd (left ventricular internal diameter in diastole; p = 0.034) and LVIDs (left ventricular internal diameter in systole; p < 0.001). In addition, a significant decrease was found in IVSs (the interventricular septum in systole; p < 0.001), LVFWs (the left ventricular free wall in systole; p = 0.002) and FS% (fractional shortening; p < 0.001). The frequency of pulmonary regurgitation was increased significantly (p < 0.001). Romifidine induced a significant increase in LVIDs (p < 0.001) and a significant decrease in IVSs (p < 0.001) and FS% (p = 0.002). Acepromazine had no significant effect upon any of the measured values. CONCLUSIONS: and clinical relevance The results indicate that sedation of horses with detomidine and to a lesser extent romifidine at the doses given in this study has a significant effect on heart function, echocardiographic measurements of heart dimensions and the occurrence of valvular regurgitation. Although the clinical significance of these results may be minimal, the potential effects of sedative drugs should be taken into account when echocardiographic variables are interpreted in clinical cases.     

Comparison of sedative effects of romifidine following intravenous, intramuscular, and sublingual administration to horses.

OBJECTIVE: To compare sedative effects of romifidine following IV, IM, or sublingual (SL) administration in horses. ANIMALS: 30 horses that required sedation for routine tooth rasping. PROCEDURE: Horses (n = 10/group) were given romifidine (120 microg/kg) IV, IM, or SL. Heart rate, respiratory rate, head height, distance between the ear tips, thickness of the upper lip, response to auditory stimulation, response to tactile stimulation, and degree of ataxia were recorded every 15 minutes for 180 minutes. Tooth rasping was performed 60 minutes after administration of romifidine, and overall adequacy of sedation was assessed. RESULTS: IV and IM administration of romifidine induced significant sedation, but SL administration did not induce significant sedative effects. Scores for overall adequacy of sedation after IV and IM sedation were not significantly different from each other but were significantly different from scores for horses given romifidine SL. Sedative and other effects varied among groups during the first 60 minutes after drug administration; thereafter, effects of IV and IM administration were similar. CONCLUSIONS AND CLINICAL RELEVANCE: Onset of action was fastest and degree of sedation was greater after IV, compared with IM, administration of romifidine, but duration of action was longer after IM administration. Sublingual administration did not result in clinically important sedative effects.     

Assessment of the sedative effects of buprenorphine administered with 10 μg/kg detomidine in horses

The aim of this randomised, observer-blinded, crossover study was to compare the effects of six treatments, administered intravenously to six horses: saline and saline (S/S); detomidine and saline (D/S); detomidine and 5 μg/kg buprenorphine (D/B5); detomidine and 7.5 μg/kg buprenorphine (D/B7.5); detomidine and 10 μg/kg buprenorphine (D/B10); and detomidine and 25 μg/kg butorphanol (D/BUT). The detomidine dose was 10 μg/kg for all treatments in which it was included. Sedation was subjectively assessed and recorded on a visual analogue scale. Peak sedation, duration of sedation and the area under the curve (AUC) for sedation scores were investigated using a univariate general linear model with post-hoc Tukey tests (P<0.05). Peak sedation and duration of sedation were statistically significantly different between treatments (P<0.001). No sedation was apparent after administration of S/S. The AUC was significantly different between treatments (P=0.010), with S/S being significantly different from D/S, D/BUT, D/B5 and D/B7.5, but not D/B10 (P=0.051).     

Pharmacokinetics of ciprofloxacin in sheep after single intravenous or intramuscular administration

Summary

The disposition and urinary excretion of ciprofloxacin (CIP) following intravenous (IV) or intramuscular (IM) administration of 7.5 mg/kg body weight in sheep (n = 5) was studied. The intravenous plasma concentration curve was best described pharmacokinetically by a two‐compartment open model, while the intramuscular administration data fitted better to a one‐compartment open model. Mean elimination half‐lives after IV and IM administration were 72 and 184 minutes, respectively. The absorption of intramuscularly administered CIP in sheep was fast: maximal plasma concentration (Cmax) was reached quickly (tmax 31.93 min) and attained values of 0.69 ± 0.27 mg/l. The bioavailability was 49%. The urinary data showed a significant decrease in the elimination rate constant of CIP when CIP was administered intramuscularly. The other parameters calculated did not display differences between the two routes of administration. The results obtained suggest that when CIP was administered by the IM route in the assayed dose, it was able to maintain serum concentrations above the MIC of most common pathogens over an 8‐hour period.     

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

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.     

Bioavailability of levamisole after intramuscular and oral administration in sheep

AIMS: To determine the bioavailability of levamisole in sheep. METHODS: Levamisole was administered to three groups of six Merino sheep orally and intramuscularly at three dose levels of 5, 7.5 and 10 mg/kg. There was a washout period of 1 week between treatments. Blood samples were collected by jugular venepuncture and plasma was separated immediately by centrifugation and stored at 20 degrees C until analysed. The levamisole concentration in plasma was determined by high performance liquid chromatography with a U.V. detection method. Individual plasma levamisole concentration-time data were analysed using the compartmental method. RESULTS: The values obtained for k(a), C(max), t(max) and F show a moderate rate and extent of absorption after oral administration of levamisole while, after intramuscular administration, these values demonstrate a high rate and extent of absorption of levamisole. The intramuscular bioavailability was higher than the oral bioavailability (rate of absorption three-fold faster, extent of absorption 25-33% higher and C(max) two-fold higher). The Friedman test involving dose and route of administration showed that the route of administration affects k(a), C(max), t(max) and F; significant differences were found in these parameters. CLINICAL RELEVANCE: On the basis of these data, the recommended routes for the administration of levamisole in sheep are oral for gastro-intestinal nematodiasis and intramuscular for extragastric nematodiasis.