Relative potency of ketamine and S(+)-ketamine in dogs

The aim of this study was to determine the relative potency of racemic ketamine and S(+)-ketamine for the hypnotic effect and to evaluate the clinical anesthesia produced by equianesthetic doses of these two substances in dogs. One hundred and eight dogs were allocated in groups R2, R2.5, R3, R6, R9, R12, S2, S2.5, S3, S6, S9, and S12, to receive by intravenous route 2, 2.5, 3, 6, 9, and 12 mg/kg of ketamine or S(+)-ketamine, respectively. A dose-effect curve was drawn with the dose logarithm and the percentage of dogs that presented hypnosis in each group. The curve was used to obtain a linear regression, to determine the effective doses 100 and the potency relationship. In another experimental phase, eight groups of five dogs received 3, 6, 9 and 12 mg/kg of ketamine or S(+)-ketamine to evaluate the periods of latency, hypnosis, and total recovery. The times in which the dogs reached the sternal position, attempted to stand up for the first time, recovered the standing position, and started to walk were also recorded. The hypnotic dose for ketamine was 9.82 +/- 3.02 (6.86-16.5) mg/kg and for S(+)-ketamine was 7.76 +/- 2.17 (5.86-11.5) mg/kg. The time of hypnosis was longer in R3 and the first attempt to stand up occurred early in R6 when compared with S3 and S6 respectively. When R9 (100% of hypnosis with ketamine) and S6 [100% of hypnosis with S(+)-ketamine] were compared (1:1.5 ratio), the time to sternal position (12 +/- 2.5 and 20.2 +/- 5.6 min respectively) and the total recovery time (45 +/- 5.5 and 60.2 +/- 5.2 min respectively) were significantly shorter with S(+)-ketamine. It was concluded that the potency ratio between ketamine and S(+)-ketamine in dogs is smaller than the one reported in other species, and that the dose obtained after a reduction of 50%, as usually performed in humans, would not be enough to obtain equianesthetic effects in dogs.

Evaluation of the adverse effects of oral firocoxib in healthy dogs

This study evaluated the adverse effects of oral firocoxib in dogs. Six dogs (20.2 +/- 6.3 kg) were studied. Values for complete blood count (CBC), serum urea, creatinine, alanine transaminase, alanine phosphatase, -glutamyl transferase, occult blood in feces, platelet aggregation, and buccal mucosal bleeding time were measured before and 7, 14, 21, and 29 days after SID treatment with firocoxib 5.3 +/- 0.34 mg/kg (FG) or lactose 1 mg/kg (LG) for 2 8 days, in a randomized crossover study. Gastrointestinal (GI) tract endoscopy was performed before treatment began and at 29 days. Lesions were scored from grade 0 to 6. Data were analyzed using ANOVA and paired t-tests (P < 0.05). None of the dogs presented adverse clinical effects. There were no significant changes in CBC, biochemical profiles within groups, or differences between groups. Pretreatment mean SD bleeding time (LG, 70.7 +/- 32.1 sec; FG, 75.8 +/- 38.1 sec) and platelet aggregation (LG, 86.4 +/- 10.2%; FG, 85.6 +/- 9.2%) were not significantly different from readings at 29 days (LG, 95.2 +/- 25 sec; FG, 91.7 +/- 24 sec and LG, 73.2 +/- 15.1%; FG, 84 +/- 10.3%) nor the groups were different. None of the dogs had positive fecal occult blood tests, and endoscopic lesion scores were grade 0 both before treatment and at 29 days. Administration of firocoxib did not cause any adverse effects on GI, or hematological or serum biochemical variables and appears to have been well tolerated by dogs.

Effects of subcutaneous methadone, morphine, buprenorphine or saline on thermal and pressure thresholds in cats

This study compared pressure and thermal thresholds after administration of three opioids in eight cats. Pressure stimulation was performed via a bracelet taped around the forearm. Three ball-bearings were advanced against the forearm by inflation of a modified blood pressure bladder. Pressure in the cuff was recorded at the end point (leg shake and head turn). Thermal threshold was tested as previously reported using a heated probe held against the thorax [Dixon et al. (2002) Research in Veterinary Science, 72, 205]. After baseline recordings, each cat received subcutaneous methadone 0.2 mg/kg, morphine 0.2 mg/kg, buprenorphine 0.02 mg/kg or saline 0.3 mL in a four period cross-over study. Measurements were made at 15, 30, 45 min and 1, 2, 3, 4, 8, 12 and 24 h after the injection. Data were analysed by ANOVA (P < 0.05). There were no significant changes in thresholds after saline. Thermal threshold increased at 45 min after buprenorphine (maximum 2.8 +/- 3 degrees C), 1-3 h after methadone (maximum 3.4 +/- 1.9 degrees C) and 45 min to 1 h (maximum 3.4 +/- 2 degrees C) after morphine. Pressure threshold increased 30-45 min (maximum 238 +/- 206 mmHg) after buprenorphine, 45-60 min after methadone (maximum 255 +/- 232 mmHg) and 45-60 min and 3-6 h (maximum 255 +/- 232 mmHg) after morphine. Morphine provided the best analgesia, and methadone appears a promising alternative. Buprenorphines limited effect was probably related to the subcutaneous route of administration. Previously, buprenorphine has produced much greater effects when given by other routes.

Effects of muscarinic receptor antagonists on acetylcholine-induced contractions of jejunal smooth muscle in horses

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Comparison of the cardio-respiratory effects of methadone and morphine in conscious dogs

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Enrofloxacin assay validation and pharmacokinetics following a single oral dose in chickens

The pharmacokinetics of enrofloxacin (ENRO), a fluoroquinolone antimicrobial agent, was studied in male broiler chickens (Cobb) after single oral administration of 10 mg of ENRO/kg b.w. A high-performance liquid chromatography-photodiode array detector (DAD) (HPLC-DAD) method was developed and validated and used for quantitation of ENRO and its major metabolite ciprofloxacin in plasma. The HPLC analyses were carried out using a cationic-octadecyl mixed column and 0.05 mol/L phosphate buffer (pH 2.5)/acetonitrile as mobile phase. The sample preparation of plasma consisted of the precipitation of proteins followed by solid phase extraction on cationic-octadecyl mixed cartridges. The method was validated considering linear range, linearity, selectivity, sensitivity, limit of detection (LOD), limit of quantitation (LOQ), intra- and inter-day precisions and accuracy. The LOD and LOQ for both fluoroquinolones were 60 and 200 ng/mL for plasma. The plasma concentration vs. time graph was characteristic of a two-compartment open model. The maximal plasma concentration of 1.5 +/- 0.2 mg/mL was achieved at 9 +/- 2 h. The elimination half-life and the mean residence time of ENRO were 1.5 +/- 0.2 and 15.64 h, respectively. The area under the concentration-time curve was calculated as 35 +/- 4 mg(.)h/mL.

Midazolam and ketamine induction before halothane anaesthesia in ponies: cardiorespiratory, endocrine and metabolic changes

Six Welsh gelding ponies were premedicated with 0.03 mg/kg of acepromazine intravenously (i.v.) prior to induction of anaesthesia with midazolam at 0.2 mg/kg and ketamine at 2 mg/kg i.v.. Anaesthesia was maintained for 2 h using 1.2% halothane concentration in oxygen. Heart rate, electrocardiograph (EGG), arterial blood pressure, respiratory rate, blood gases, temperature, haematocrit, plasma arginine vasopressin (AVP), dynorphin, beta-endorphin, adrenocorticotropic hormone (ACTH), cortisol, dopamine, noradrenaline, adrenaline, glucose and lactate concentrations were measured before and after premedication, immediately after induction, every 20 min during anaesthesia, and at 20 and 120 min after disconnection. Induction was rapid, excitement-free and good muscle relaxation was observed. There were no changes in heart and respiratory rates, Decrease in temperature, hyperoxia and respiratory acidosis developed during anaesthesia and slight hypotension was observed (minimum value 76 +/- 10 mm Hg at 40 mins), No changes were observed in dynorphin, beta-endorphin, ACTH, catecholamines and glucose, Plasma cortisol concentration increased from 220 +/- 17 basal to 354 +/- 22 nmol/L at 120 min during anaesthesia; plasma AVP concentration increased from 3 +/- 1 basal to 346 +/- 64 pmol/L at 100 min during anaesthesia and plasma lactate concentration increased from 1.22 +/- 0.08 basal to 1.76 +/- 0.13 mmol/L at 80 min during anaesthesia, Recovery was rapid and uneventful with ponies taking 46 +/- 6 min to stand. When midazolam/ketamine was compared with thiopentone or detomidine/ketamine for induction before halothane anaesthesia using an otherwise similar protocol in the same ponies, it caused slightly more respiratory depression, but less hypotension. Additionally, midazolam reduced the hormonal stress response commonly observed during halothane anaesthesia and appears to have a good potential for use in horses.

Development and characterization of an equine behaviour chamber and the effects of amitraz and detomidine on spontaneous locomotor activity

This report describes the development of a behaviour chamber and the validation of the chamber to measure locomotor activity of a horse, Locomotor activity was detected by four Mini-beam sensors and recorded on a data logger every 5 min for 22 h. Horses were more active during daytime than in the evening, which was at least partially related to human activity in their surroundings. To validate the ability of the chambers to detect changes in activity, fentanyl citrate and xylazine HCl, agents well-characterized as a stimulant and a depressant, respectively, were administered to five horses. Fentanyl citrate (0.016 mg/kg) significantly increased locomotor activity which persisted for 30 min, Xylazine HCl (1 mg/kg) significantly reduced locomotor activity for 90 min. Amitraz produced a dose-dependent decrease in locomotor activity, lasting 75 min for the 0.05 mg/kg dose, 120 min for the 0.10 mg/kg dose, and 180 min for the 0.15 mg/kg dose, In a separate experiment, yohimbine administration immediately reversed the sedative effect of amitraz, This suggests there is a similarity in the mode of action of amitraz, xylazine and detomidine, as yohimbine acts primarily by blocking central alpha 2-adrenoceptors that are stimulated by agents like xylazine, There was also a significant decrease in locomotor activity following injection of detomidine (0.02, 0.04 and 0.08 mg/kg) for 1.5, 3.5 and 5.0 h, respectively, the locomotor chamber is a useful, sensitive and highly reproducible tool for measuring spontaneous locomotor activity in the horse, which allows investigators to determine an agent's average time of onset, duration and intensity of effect on movement.

Pharmacokinetics of a new long acting endectocide formulation containing 2.25% ivermectin and 1.25% abamectin in cattle

The objective of this study was to determine the kinetic parameters of a new formulation that contained 2.25% ivermectin combined with 1.25% abamectin in bovine plasma. The results for 2.25% ivermectin: C-max (37.11 ng/mL +/- 7.42), T-max (16 days +/- 5.29), T-1/2 (44.62 days +/- 53.89), AUC (928.2 ng.day/mL +/- 153.83) and MRT (36.73 days +/- 33.64), and for 1.25% abamectin: C-max (28.70 ng/mL +/- 9.54), T-max (14 days +/- 4.04), T-1/2 (15.40 days +/- 11.43), AUC (618.05 ng.day/mL +/- 80.27) and MRT (20.79 days +/- 8.43) suggest that this combination of 2.25% ivermectin + 1.25% abamectin possesses properties that give this pharmaceutical formula a longer activity time than two of the commercial products tested (1% ivermectin and 1% abamectin), and showed similarity to 3.15% ivermectin.