Plasma concentrations of buprenorphine following a single subcutaneous administration of a sustained release formulation of buprenorphine in sheep.

The goal of the present study was to evaluate the potential use of slow release buprenorphine in sheep. Twelve adult female sheep (6 Dorset and 6 Suffolk, 12 months of age) were used for this project and were divided into 2 experimental groups (n = 6/group comprising 3 Dorset and 3 Suffolk sheep). Sustained release (SR) buprenorphine was administered subcutaneously in the scapular region at a concentration of 0.1 mg/kg body weight (BW) for group 1 and of 0.05 mg/kg BW for group 2. Following blood collections at selected time points, plasma concentrations of buprenorphine was performed by tandem liquid chromatograph-mass spectrometry. Mean buprenorphine concentration was above 0.1 ng/mL at 48 h up to 192 h post-injection for group 1 and it was above 0.1 ng/mL at 48 h up to 72 h post-injection for group 2. In conclusion, a long lasting potential analgesic plasma level of buprenorphine is attained following a single subcutaneous injection of 0.1 mg/kg BW of SR buprenorphine in sheep. However the effective analgesic plasma threshold still needs to be determined in sheep.

L'objectif de la présente étude était d'évaluer l'utilisation potentielle de buprénorphine à relâchement lent (RL) chez le mouton. Douze brebis adultes (6 Dorset et 6 Suffolk, 12 mois d'âge) ont été utilisées pour ce projet et ont été réparties en deux groupes expérimentaux (n = 6/groupe, 3 Dorset et 3 Suffolk). De la buprénorphine à relâchement continu a été administrée par voie sous-cutanée dans la région scapulaire à une concentration de 0,1 mg/kg de poids corporel (PC) pour le groupe 1 et à 0,05 mg/kg de PC pour le groupe 2. Suite à des prélèvements sanguins à des moments sélectionnés, les concentrations plasmatiques de buprénorphine ont été déterminées par spectrométrie de masse en tandem avec la chromatographie en phase liquide. La concentration moyenne de buprénorphine était supérieure à 0,1 ng/mL après 48 h et jusqu'à 192 h post-injection pour le groupe 1, et était supérieure à 0,1 ng/mL après 48 et jusqu'à 72 h post-injection pour le groupe 2. En conclusion, un niveau plasmatique prolongé de buprénorphine avec un potentiel analgésique est atteint suite à une injection sous-cutanée unique de 0,1 mg/kg de PC de buprénorphine RL chez le mouton. Toutefois, le seuil plasmatique analgésique réel demeure encore à être déterminé chez le mouton.(Traduit par Docteur Serge Messier).

Physiological and pharmacokinetic effects of multilevel caging on Sprague Dawley rats under ketamine-xylazine anesthesia.

While the cage refinement is a necessary step towards improving the welfare of research rats, increasing the complexity and surface area of the living space of an animal may have physiological impacts that need to be taken into consideration. In this study, ketamine (80 mg/kg) and xylazine (10 mg/kg) caused a short duration anesthesia that was significantly decreased in Sprague-Dawley rats housed in multilevel cages (MLC), compared to rats housed in standard cages (SDC). The withdrawal reflex, the palpebral reflexes and the time-to-sternal all occurred earlier in MLC housed rats, suggesting an effect of housing on the physiology of the rats. In addition, during anesthesia, cardiac frequencies were increased in animals housed in the smaller SDC. Respiratory frequencies, the blood oxygen saturation and rectal temperatures during anesthesia did not vary between conditions during the anesthesia. While xylazine pharmacokinetics were unchanged with caging conditions, the clearance and half-lives of ketamine and its metabolite, norketamine, were altered in the rats housed in MLC. Finally, while no difference was ultimately seen in rat body weights, isolated liver and adrenal gland weights were significantly lighter in rats housed in the MLC. Increasing cage sizes, while having a positive impact on wellbeing in rats, can alter anesthetic drug metabolism and thus modify anesthesia parameters and associated physiological processes.

Assessment of stability of ketamine-xylazine preparations with or without acepromazine using high performance liquid chromatography-mass spectrometry.

The objective of this study was to evaluate the stability of 3 distinct preparations of ketamine and xylazine, with or without acepromazine, stored at room temperature or at 4°C for 1, 2, and 3 mo. Drug concentrations were compared to fresh solutions, using a high performance liquid chromatography-mass spectrometry/selected-ion monitoring (HPLC-MS/SIM) assay. The concentrations of ketamine and xylazine, diluted in physiological saline, did not change over time at room temperature or at 4°C. However, acepromazine concentrations decreased over time when stored at room temperature. In contrast, undiluted ketamine-xylazine preparations gradually decreased in concentration when stored at room temperature. All of the drug concentrations remained above 90% of their original concentration when stored at 4°C. In conclusion, when diluted in physiological saline, ketamine-xylazine cocktails can be stored for 3 mo, whereas undiluted cocktails can lose efficacy over 3 mo at room temperature. Storage at 4°C could preserve drug stability.

Cette étude vise à évaluer la stabilité de trois préparations de kétamine et xylazine avec ou sans acépromazine gardées à température pièce, ou à 4°C, pour 1, 2 et 3 mois. Les concentrations des drogues ont été comparées à des solutions fraiches, toutes analysées par HPLC-MS/SIM. Les concentrations de kétamine et xylazine, des solutions diluées dans la saline physiologique, sont restées constantes indépendamment du temps et de la température de conservation, par contre la concentration d'acépromazine a diminué dans les préparations gardées à température pièce. En contraste, les concentrations des préparations pures de kétamine et xylazine conservées à température pièce ont diminué avec le temps. En conclusion, la kétamine et la xylazine en cocktail avec du salin peuvent être utilisés pour une période de 3 mois, par contre, conservées à température pièce, les concentrations diminuent progressivement en préparation pure. La conservation des préparations à 4°C favorise la stabilité des drogues.(Traduit par les auteurs).

Evaluation of the anesthetic effects of MS222 in the adult Mexican axolotl (Ambystoma mexicanum).

The Mexican axolotl (Ambystoma mexicanum) is a unique research model in several fields of medicine, where surgical and invasive procedures may be required. As yet, little is known about the efficacy of MS222 (tricaine methanesulfonate), which is the most commonly used anesthetic agent in amphibians. The main objectives of this study were to evaluate the anesthetic effects and physiological changes in adult axolotls following a 20-minute immersion bath, containing progressive MS222 concentrations starting at 0.1%. Depth of anesthesia and physiological changes were evaluated every 15 minutes post-MS222 exposure with the following parameters: righting behavior, withdrawal reflex, acetic acid test response, heart rate, and blood oxygen saturation, as well as cloacal and body surface temperatures. A 20-minute exposure in a 0.1% MS222 immersion bath (n=6 animals) had no anesthetic effects on adult axolotls after 20 minutes of exposure. With a 0.2% MS222 solution, all axolotls (n=9) were deeply anesthetized at 15 minutes, and 80% were still unresponsive at 30 minutes postexposure. Blood oxygen saturation and heart rate were slightly, but significantly, increased when compared with the baseline value and remained stable up to recovery. There was no significant increase in surface and cloaca temperatures, compared with baseline. With the 0.4% MS222 solution, the duration of anesthesia lasted for 90 minutes to at least 120 minutes (n=3 animals) and this concentration was deemed too high. In conclusion, a 20-minute immersion bath with 0.2% MS222 may be used for short procedures (15-30 minutes) requiring anesthesia of adult axolotls.

Effects of α2-adrenergic drugs on small intestinal motility in the horse: an in vitro study.

The effects of selective α(2)-agonists (xylazine, detomidine and medetomidine) and antagonists (yohimbine and atipamezole) on in vitro small intestine motility in the horse were evaluated. Samples of equine jejunum were placed in isolated organ baths and drug-induced modifications of motility were measured by means of an isotonic transducer. All tested α(2)-agonists dose-dependently reduced both spontaneous and electrically-evoked phasic contractions. Conversely, α(2)-antagonists were ineffective when tested alone, and showed a heterogeneous and dose-independent ability to inhibit agonist activity. In particular, the antagonism exerted by higher concentrations of both yohimbine and atipamezole against α(2)-agonists was weaker than when lower concentrations were used. The data are indicative of the presence of both pre- and post-synaptic α(2)-adrenoceptors with inhibitory activity on equine jejunum motility, and support a possible therapeutic utility of these drugs in horse intestinal disorders associated with hypermotility.

Protective effects of proton pump inhibitors against indomethacin-induced lesions in the rat small intestine.

Proton pump inhibitors (PPIs) have been shown to be effective in preventing gastric and duodenal ulcers in high-risk patients taking nonsteroidal anti-inflammatory drugs (NSAIDs); by contrast, scarce information is available concerning the effects of PPIs on intestinal damage induced by NSAIDs in humans or in experimental animals. We examined the effects of lansoprazole and omeprazole on the intestinal injury induced by indomethacin in the conscious rat. PPIs were administered by the intragastric route at 30, 60 and 90 micromol/kg, 12 h and 30 min before and 6 h after indomethacin treatment. The effects of omeprazole and lansoprazole were evaluated on: (1) macroscopic and histologic damage; (2) mucosal polymorphonuclear cell infiltration; (3) oxidative tissue damage and (4) bacterial translocation from lumen into the intestinal mucosa. Lansoprazole and omeprazole (at 90 micromol/kg) significantly decreased (P<0.01) the macroscopic and histologic damage induced by indomethacin in the rat small intestine. Furthermore, both drugs greatly reduced (P<0.01) the associated increases in myeloperoxidase levels and lipid peroxidation induced by indomethacin, whereas they only moderately affected (P<0.05) the translocation of enterobacteria from lumen into the intestinal mucosa. These data demonstrate that omeprazole and lansoprazole can protect the small intestine from the damage induced by indomethacin in the conscious rat. The intestinal protection, possibly related to antioxidant and anti-inflammatory properties of these drugs, may suggest new therapeutic uses of PPIs in intestinal inflammatory diseases.