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1.

Objective

To evaluate dexmedetomidine, midazolam and dexmedetomidine–midazolam for sedation and antinociception in tegus.

Study design

Prospective, crossover, randomized, blinded study.

Animals

Six healthy tegus (Salvator merianae) weighing 1.6 ± 0.3 kg.

Methods

Tegus were administered intramuscularly saline (0.5 mL; CON), dexmedetomidine (0.2 mg kg?1; DX), midazolam (1 mg kg?1; MZ) and dexmedetomidine–midazolam (same doses; DM). Heart rate (HR) and respiratory frequency (fR) were recorded before treatment (baseline) and 15, 30 minutes, 1, 2, 3, 4, 6, 8, 12 and 24 hours after the treatments. Sedation scores were recorded according to resistance to manual restraint, posture and response to noxious stimulus, at baseline and 5, 10, 15, 30 minutes, 1, 2, 3, 4, 6, 8, 12 and 24 hours after the treatments. Antinociception was evaluated by measurement of latency of limb withdrawal reflex (LWR) to thermal stimulus, recorded at baseline and 15 minutes, 1, 2, 4, 8, 12 and 24 hours after the treatments.

Results

Lower HR (DX and DM) and fR (MZ, DX and DM) than CON were measured 15 minutes after the treatment and for up to 6 hours. Sedation was mild to moderate in MZ, deep in DM and absent in DX, although animals showed behavioral changes in DX, with increase in aggressiveness. Median (interquartile range) duration of sedation were 170 (50; 235) minutes in MZ and 230 (115; 235) minutes in DM. Recovery period was prolonged in both treatments, surpassing the duration of the experiment. Higher LWR than CON was detected from 15 minutes until 12 hours in DX and DM.

Conclusions and clinical relevance

Midazolam provided sedation without antinociception, and dexmedetomidine provided antinociception without sedation. Drug combination increased the duration of sedation but not antinociception. Due to increased duration of sedation, reversal of effects with flumazenil and atipamezole should be considered after conclusion of clinical procedures.  相似文献   

2.
ObjectiveTo compare the sedative and cardiopulmonary effects of intranasal (IN) and intramuscular (IM) administration of dexmedetomidine and midazolam combination in New Zealand White rabbits.Study designA randomized, crossover experimental study.AnimalsA total of eight healthy New Zealand White rabbits, aged 6–12 months, weighing 3.1 ± 0.3 kg (mean ± standard deviation).MethodsThe animals were randomly assigned to administration of dexmedetomidine (0.1 mg kg–1) with midazolam (2 mg kg–1) by either IN or IM route separated by 2 weeks. The electrocardiogram, pulse rate (PR), peripheral haemoglobin oxygen saturation (SpO2), mean noninvasive arterial pressure (MAP), respiratory frequency (fR) and rectal temperature were measured before drug administration (baseline), T0 (onset of sedation) and at 5 minute intervals until recovery. The onset of sedation, duration of sedation and sedation score (SS) were also recorded.ResultsThe PR was significantly lower in treatment IM than in treatment IN over time (p = 0.027). MAP < 60 mmHg developed in two and four rabbits in treatments IN and IM, respectively. SpO2 progressively decreased over time in both treatments. fR was lower than baseline at several time points in both treatments. Onset of sedation was shorter in treatment IN (90 ± 21 seconds) than in treatment IM (300 ± 68 seconds) (p = 0.036). Duration of sedation was longer in treatment IM (55.2 ± 8.7 minutes) than in treatment IN (39.6 ± 2.1 minutes) (p = 0.047). No significant difference in SS was observed between treatments (p > 0.05).Conclusions and clinical relevanceCombination of dexmedetomidine (0.1 mg kg–1) and midazolam (2 mg kg–1) decreased fR, PR and SpO2 regardless of the administration route in New Zealand White rabbits. A more rapid action and shorter duration of sedation were observed after treatment IN than after treatment IM administration.  相似文献   

3.
4.
Intravenous alfaxalone, administered at a dose of 5 mg/kg in the jugular vein, was evaluated in 20 leopard geckos (Eublepharis macularius) to ascertain its ability to provide anesthesia. The induction time, time to loss of mandibular tone, interval of deep anesthesia, and full recovery time were 27.5 ± 30.7 seconds (10 to 56 seconds), 1.3 ± 1.4 minutes (11 seconds to 4 minutes), 12.5 ± 2.2 minutes (11.11 to 15.39 minutes), and 18.8 ± 12.1 minutes (10.4 to 52.31 minutes), respectively. A significant reduction in heart rate (74 ± 12.9 beats/minute) was recorded between 2 and 24 minutes after alfaxalone administration. A significant decrease in respiratory rate (26.8 ± 10.1 breaths/minute) was recorded 2 minutes after alfaxalone administration, and respiratory rate remained lower than the basal rate (31.4 ± 3.1 breaths/minute) for 24 minutes but without statistical significance. The intravenous administration of alfaxalone in leopard geckos achieved a rapid onset of anesthesia and a suitable recovery time. Based on this investigation, an afaxalone dose of 5 mg/kg intravenously proved to be suitable for sedation before tracheal intubation. Moreover, the administration route via the jugular vein, was acceptable in leopard geckos; a species in which other venipuncture sites can be challenging or inaccessible.  相似文献   

5.

Objective

To study the effects of MK-467, a peripheral α2-adrenoceptor antagonist, on sedation, heart rate and blood pressure after intramuscular (IM) coadministration with 25 μg kg?1 of dexmedetomidine in cats.

Study design

Prospective, randomized, controlled, blinded, cross-over, experimental study.

Animals

A total of eight healthy, adult, neutered male cats.

Methods

Cats were administered five IM treatments at least 2 weeks apart, consisting of dexmedetomidine 25 μg kg?1 (D25), MK-467 600 μg kg?1 (M600) and D25 combined with 300, 600 and 1200 μg kg?1 of MK-467 (D25M300, D25M600 and D25M1200, respectively). Heart rate and direct arterial blood pressure were recorded via telemetry and sedation assessed prior to treatments and at intervals for 8 hours thereafter.

Results

Heart rate decreased significantly after all treatments with dexmedetomidine and remained below baseline up to 240 (D25), 20 (D25M300) and 3 minutes (D25M600 and D25M1200). Mean arterial pressure (MAP) increased with D25, remained unchanged with M600 and decreased over time with all combination treatments. The highest and lowest MAP after each treatment were 168 ± 17 and 100 ± 14 (D25), 157 ± 18 and 79 ± 11 (D25M300), 153 ± 11 and 74 ± 10 (D25M600), 144 ± 12 and 69 ± 7 (D25M1200) and 136 ± 9 and 104 ± 13 mmHg (M600). All treatments with dexmedetomidine produced sedation although its duration was significantly reduced by the addition of MK-467.

Conclusions and clinical relevance

Dexmedetomidine induced bradycardia and hypertension, which were attenuated by all three doses of MK-467. The duration of sedation was reduced by MK-467. MK-467 may improve the cardiovascular tolerance of IM dexmedetomidine in cats.  相似文献   

6.
OBJECTIVE: To evaluate the effects of intranasal administration of midazolam and xylazine (with or without ketamine) and detomidine and their specific antagonists in parakeets. DESIGN: Prospective study. ANIMALS: 17 healthy adult Ring-necked Parakeets (Psittacula krameri) of both sexes (mean weight, 128.83+/-10.46 g [0.28+/-0.02 lb]). PROCEDURE: The dose of each drug or ketamine-drug combination administered intranasally that resulted in adequate sedation (ie, unrestrained dorsal recumbency maintained for >or=5 minutes) was determined; the onset of action, duration of dorsal recumbency, and duration of sedation associated with these treatments were evaluated. The efficacy of the reversal agents flumazenil, yohimbine, and atipamezole was also evaluated. RESULTS: In parakeets, intranasal administration of midazolam (7.3 mg/kg [3.32 mg/lb]) or detomidine (12 mg/kg [5.45 mg/lb]) caused adequate sedation within 2.7 and 3.5 minutes, respectively. Combinations of midazolam (3.65 mg/kg [1.66 mg/lb]) and xylazine (10 mg/kg [4.55 mg/lb]) with ketamine (40 to 50 mg/kg [18.2 to 22.7 mg/lb]) also achieved adequate sedation. Compared with detomidine, duration of dorsal recumbency was significantly longer with midazolam. Intranasal administration of flumazenil (0.13 mg/kg [0.06 mg/lb]) significantly decreased midazolam-associated recumbency time. Compared with the xylazineketamine combination, duration of dorsal recumbency was longer after midazolam-ketamine administration. Intranasal administration of flumazenil, yohimbine, or atipamezole significantly decreased the duration of sedation induced by midazolam, xylazine, or detomidine, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Intranasal administration of sedative drugs appears to be an acceptable method of drug delivery in Ring-necked Parakeets. Reversal agents are also effective when administered via this route.  相似文献   

7.
The study compared limb-to-lung circulation times (CT) in dogs under general anaesthesia after premedication with dexmedetomidine (DEX) or acepromazine–methadone (ACE–M). Healthy male and female dogs (n = 20) were randomly assigned to receive acepromazine 0.04 mg/kg and methadone 0.2 mg/kg intramuscularly (IM), or DEX 0.01 mg/kg IM. Anesthesia was induced with propofol and maintained with isoflurane at similar concentration in both groups. Mechanical ventilation was started immediately (20 breaths/min; inspiratory to expiratory ratio 1:2) and tidal volume was adjusted to achieve an end-tidal CO2 concentration (PE’CO2) of between 3.9 and 5.3 kPa. Ten minutes later arterial blood gas was analyzed and baseline data recorded for 3 minutes. A single dose of sodium bicarbonate 0,5 mEq/kg was administered intravenously over 10 s starting with inspiration. Limb-to-lung CT was defined as the time interval between the start of bicarbonate injection and the recording of the highest PE’CO2.Following bicarbonate administration, PE’CO2 increased, and then rapidly decreased to baseline in both groups. CT was shorter in the ACE–M group (20 ± 2.3 vs. 27 ± 5.1 s). Bodyweight was higher in the ACE–M group (30.6 ± 3.9 vs. 23.3 ± 6.8 kg). Mean arterial blood pressure was higher in the DEX group (92 ± 9 vs. 73 ± 7 mm Hg) but premedication with DEX significantly prolonged CT compared to premedication with ACE–M.  相似文献   

8.

Objective

To determine the intubation dose and select physiologic effects of alfaxalone alone or in combination with midazolam or ketamine in dogs.

Study design

Prospective, clinical study.

Animals

Fifty-three healthy client-owned dogs [mean ± standard deviation (SD)] 5.1 ± 1.8 years, 27 ± 15.4 kg, scheduled for elective orthopedic surgery.

Methods

After premedication with acepromazine (0.02 mg kg–1) and hydromorphone (0.1 mg kg–1) intramuscularly, alfaxalone (0.25 mg kg–1) was administered intravenously over 15 seconds followed immediately by 0.9% saline (AS), midazolam (0.3 mg kg–1; AM), ketamine (1 mg kg–1; AK1), or ketamine (2 mg kg–1; AK2). Additional alfaxalone (0.25 mg kg–1 increments) was administered as required to permit endotracheal intubation. The incidence of apnea and the time from intubation until spontaneous movement were recorded. Heart rate (HR) and blood pressure were recorded 15 minutes after premedication, after intubation and 2, 5, 10 and 15 minutes thereafter. Blood was collected for measurement of serum glucose and insulin concentrations before induction, after intubation and at 2, 5, 10 and 50 minutes. Data were analyzed by split-plot anova with Bonferroni adjustment for the number of group comparisons.

Results

Mean ± SD alfaxalone mg kg–1 doses required for endotracheal intubation were AS (1.0 ± 0.4), AM (0.4 ± 0.2), AK1 (0.5 ± 0.3) and AK2 (0.5 ± 0.4) (p = 0.0005). Differences in cardiopulmonary variables among groups were minor; HR decreased in AS, while in other groups, HR increased transiently postintubation. Incidence of apnea in AS was 54% with no significant difference among groups. Midazolam significantly prolonged time from intubation until spontaneous movement (p < 0.002).

Conclusions and clinical relevance

Midazolam and ketamine reduced the alfaxalone dose required for endotracheal intubation. Serum glucose and insulin concentrations were not influenced by administration of alfaxalone alone or when administered with midazolam or ketamine.  相似文献   

9.
The purpose of this study was to assess the pharmacokinetics of gabapentin in healthy greyhound dogs after single oral doses targeted at 10 and 20 mg/kg PO. Six healthy greyhounds were enrolled (3 males, 3 females). Blood was obtained at predetermined times for the measurement of gabapentin plasma concentrations by liquid chromatography/mass spectrometry. Pharmacokinetic parameters were determined with computer software.The actual mean (and range) doses administered were 10.2 (9.1–12.0) mg/kg and 20.5 (18.2–24) mg/kg for the 10 mg/kg and 20 mg/kg targeted dose groups. The mean CMAX for the 10 and 20 mg/kg groups were 8.54 and 13.22 μg/mL at 1.3 and 1.5 h, and the terminal half-lives were 3.3 and 3.4 h, respectively. The relative bioavailability of the 10 mg/kg group was 1.13 compared to the 20 mg/kg group. Gabapentin was rapidly absorbed and eliminated in dogs, indicating that frequent dosing is needed to maintain minimum targeted plasma concentrations.  相似文献   

10.
ABSTRACT

Aim: To evaluate the sedative and clinical effects of I/V xylazine, detomidine, medetomidine and dexmedetomidine in miniature donkeys.

Methods: Seven clinically healthy, male adult miniature donkeys with a mean age of 6 years and weight of 105?kg, were assigned to five I/V treatments in a randomised, cross-over design. They received either 1.1?mg/kg xylazine, 20?μg/kg detomidine, 10?μg/kg medetomidine, 5?μg/kg dexmedetomidine or saline, with a washout period of ≥7 days. The degree of sedation was scored using a 4-point scale by three observers, and heart rate (HR), respiration rate (RR), rectal temperature and capillary refill time (CRT) were recorded immediately before and 5, 10, 15, 30, 60, 90 and 120 minutes after drug administration.

Results: All saline-treated donkeys showed no sedation at any time, whereas the donkeys treated with xylazine, detomidine, medetomidine and dexmedetomidine had mild or moderate sedation between 5 and 60 minutes after treatment, and no sedation after 90 minutes. All animals recovered from sedation without complication within 2 hours. The mean HR and RR of saline-treated donkeys did not change between 0 and 120 minutes after administration, but the mean HR and RR of donkeys treated with xylazine, detomidine, medetomidine and dexmedetomidine declined between 5 and 60 minutes after drug administration. The mean rectal temperature of all treated donkeys did not change between 0 and 120 minutes after administration. The CRT for all donkeys was ≤2 seconds at all times following each treatment.

Conclusions and clinical relevance: Administration of xylazine at 1.1?mg/kg, detomidine at 20?μg/kg, medetomidine at 10?μg/kg and dexmedetomidine at 5?μg/kg resulted in similar sedation in miniature donkeys. Therefore any of the studied drugs could be used for sedation in healthy miniature donkeys.  相似文献   

11.
Two experiments were conducted to determine the effects of pre-weaning vitamin E, Se, and Cu supplementation on performance and immune response in stressed calves. In Exp. 1, 71 Hereford x Angus calves were individually creep fed: 1) control supplement (CON), 2) control plus 500 IU vitamin E + 0.3 mg Se/kg DM (E), 3) control plus 10 mg Cu/kg DM (CU), or 4) a combination of E and CU treatments (ECU). In Exp. 2, 80 Hereford (Angus calves were individually creep fed: 1) control supplement (CON), 2) control plus 0.3 mg Se/kg DM (SE), 3) control plus 500 IU vitamin E + 0.3 mg Se/kg DM (LOWE), 4) control plus 1000 IU vitamin E + 0.3 mg Se/kg DM (MEDE), or 5) control plus 1500 IU vitamin E + 0.3 mg Se/kg DM (HIE). Treatments continued for 49 (Exp. 1) or 53 d (Exp. 2) prior to weaning. At weaning all calves were transported to feedlot facilities. In Exp. 1, vitamin E tended (P<0.09) to improve post-weaning ADG and reduce (P<0.06) plasma haptoglobin (Hp), but had no effect on plasma α-tocopherol. Dietary Cu tended to increase (P<0.01) liver Cu stores, and antibody titers to bovine viral diarrhea (BVD) were greater (P<0.04) at weaning in CU and E calves. In Exp. 2, vitamin E tended to increase serum α-tocopherol (P<0.06) and cortisol (P<0.08). Vitamin E and Se supplementation may improve post-weaning performance and decrease plasma Hp concentrations in stressed calves.  相似文献   

12.
ObjectiveTo compare effects of four drug combinations on sedation, echocardiographic, haematologic and biochemical variables and recovery in cats.Study designExperimental randomized ‘blinded’ cross-over study.AnimalsSix healthy cats.Materials and MethodsTreatments were administered intramuscularly: midazolam 0.4 mg kg?1 and butorphanol 0.4 mg kg?1 (MB); midazolam 0.4 mg kg?1, butorphanol 0.4 mg kg?1 and ketamine 3 mg kg?1 (MBK); midazolam 0.4 mg kg?1, butorphanol 0.4 mg kg?1 and dexmedetomidine 5 μg kg?1 (MBD); ketamine 3 mg kg?1 and dexmedetomidine 5 μg kg?1(KD). Sedation was evaluated at time-points over 10 minutes post injection. Echocardiography, systolic arterial blood pressure (SAP) measurement and blood sampling were performed at baseline and from 10 minutes after treatment. Quality of recovery was scored. Data were analysed by anova for repeated measures. p < 0.05 was considered significant.ResultsThe lowest sedation score was obtained by MB, (median 10.5 [7; 20]), highest by KD (36.5 [32; 38]). Quality of recovery was best with KD (0.5 [0; 2]), and worst with MB (7.5 [4; 11]). Relative to baseline measurements, treatments decreased SAP by 17%, 25%, 13%, 5% in MB, MBK, MBD and KD, respectively. Heart rate decreased (p < 0.05) after MBD (44%) and KD (34%). All treatments decreased stroke volume by 24%, 21%, 24%, 36%, and cardiac output by 23%, 34%, 54%, 53% in MB, MBK, MBD and KD, respectively. Packed cell volume was decreased (p < 0.05) by 20%, 31%, 29% in MBK, MBD and KD, respectively. Plasma glucose was increased after MBD (31%) and KD (52%) and lactate concentration was decreased (p < 0.05) after MBK (58%), MBD (72%) and KD (65%).Conclusions and clinical relevanceThe MB combination did not produce sedation in healthy cats. Treatment MBK led to acceptable sedation and minimal cardiovascular changes. Both treatments with dexmedetomidine produced excellent sedation and recovery but induced more cardiovascular depression and haematologic changes.  相似文献   

13.
The aim of this study was to characterise the pharmacokinetic properties of different formulations of erythromycin in cats. Erythromycin was administered as lactobionate (4 mg/kg intravenously (IV)), base (10 mg/kg, intramuscularly (IM)) and ethylsuccinate tablets or suspension (15 mg/kg orally (PO)). After IV administration, the major pharmacokinetic parameters were (mean ± SD): area under the curve (AUC)(0–∞) 2.61 ± 1.52 μg h/mL; volume of distribution (Vz) 2.34 ± 1.76 L/kg; total body clearance (Clt) 2.10 ± 1.37 L/h kg; elimination half-life (t½λ) 0.75 ± 0.09 h and mean residence time (MRT) 0.88 ± 0.13 h. After IM administration, the principal pharmacokinetic parameters were (mean ± DS): peak concentration (Cmax), 3.54 ± 2.16 μg/mL; time of peak (Tmax), 1.22 ± 0.67 h; t½λ, 1.94 ± 0.21 h and MRT, 3.50 ± 0.82 h. The administration of erythromycin ethylsuccinate (tablets and suspension) did not result in measurable serum concentrations. After IM and IV administrations, erythromycin serum concentrations were above minimum inhibitory concentration (MIC)90 = 0.5 μg/mL for 7 and 1.5 h, respectively. However, these results should be interpreted cautiously since tissue erythromycin concentrations have not been measured and can reach much higher concentrations than in blood, which may be associated with enhanced clinical efficacy.  相似文献   

14.
Aristida purpurea (purple threeawn) is a competitive native perennial grass with monoculturistic tendencies and poor palatability. We examined effects of fire, defoliation, and interspecific/intraspecific planting for 1) threeawn responses in the presence of threeawn, Bouteloua gracilis, or Pascopyrum smithii, and 2) B. gracilis and P. smithii response with threeawn. Biomass, aboveground production, tillers, and axillary buds were analyzed following two fire and four clipping treatments applied to three species–pair combinations in a completely randomized factorial design with nine replications. Fire killed 36% of threeawn. Fire reduced surviving threeawn biomass 61% and reduced production 27%. Threeawn production was greatest when neither plant was clipped and least when competing species were moderately clipped, or when both plants were severely clipped. Tiller counts of burned threeawn were similar among clipping treatments, and less than non-clipped or moderately clipped plants not burned. Fire decreased threeawn axillary buds on average by 25%. Moderately clipped plants had greater production than those from other clipping treatments across species. Average threeawn percentage of pot biomass was greater with B. gracilis (46 ± 3% SE) than P. smithii (38 ± 3% SE). Fire reduced threeawn from 60 ± 3% to 23 ± 3% of pot biomass, indicating good potential for rapid reductions in threeawn dominance and restoration of plant diversity with fire.  相似文献   

15.
The aim of this study was to determine the pharmacokinetics of dexamethasone in broiler chickens. Dexamethasone sodium phosphate (0.3 mg/kg bodyweight) was injected IV or IM and blood samples were collected at 0, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12 and 24 h after administration. Dexamethasone in the plasma samples was measured using a liquid chromatography–tandem mass spectrometry method and the pharmacokinetics analysed according to a one-compartmental model.The maximum plasma concentration after IM administration occurred at 0.37 h. The elimination half-life for dexamethasone was 0.46 h and 0.70 h following IV and IM administration, respectively, which was shorter than other species, while the clearance (1.26 L/h kg) was higher than has been reported for other species (<0.5 L/h kg). The volume of distribution (~1 L/kg) was similar to values reported for other species and the bioavailability of dexamethasone after IM administration was 100%. The results from this study will be useful in investigating whether inflammatory disease may affect the pharmacokinetic parameters of dexamethasone in chickens.  相似文献   

16.

Objective

To compare postanesthetic xylazine and dexmedetomidine on recovery characteristics from sevoflurane anesthesia in horses.

Study design

Randomized, crossover study.

Animals

Six geldings, mean ± standard deviation (SD) (range), 17 ± 4 (11–24) years and 527 ± 80 (420–660) kg.

Methods

Horses were anesthetized with sevoflurane for 60 minutes under standardized conditions for a regional limb perfusion study. In recovery, horses were administered either xylazine (200 μg kg?1) or dexmedetomidine (0.875 μg kg?1) intravenously. Recoveries were unassisted and were video-recorded for later evaluation of recovery events and quality by two individuals unaware of treatment allocation. Recovery quality was assessed using a 100 mm visual analog scale (VAS) (0 = poor recovery, 100 = excellent recovery), the Edinburgh Scoring System (ESS) (0–100; 100 = excellent recovery) and the mean attempt interval (MAI) (longer = better). Data are mean ± SD.

Results

All recovery quality assessments (xylazine and dexmedetomidine, respectively: VAS: 71 ± 21 mm, 84 ± 13 mm; ESS: 65 ± 22, 67 ± 30; MAI: 52 ± 24 minutes, 60 ± 32 minutes) and events (first limb movement: 37 ± 8 minutes, 42 ± 10 minutes; first attempt to lift head: 44 ± 12 minutes, 48 ± 9 minutes; first attempt to sternal posture: 57 ± 28 minutes, 50 ± 7 minutes; number of head bangs: 2.0 ± 3.0, 0.5 ± 0.5; time to first attempt to stand: 72 ± 6 minutes, 78 ± 13 minutes; time to standing: 79 ± 14 minutes, 84 ± 13 minutes) did not differ significantly between treatments (p > 0.05).

Conclusions and clinical relevance

Recovery characteristics did not differ significantly between postanesthetic xylazine and dexmedetomidine following 1 hour of sevoflurane anesthesia in horses in this study. Further evaluations in more horses and in younger horses are required to confirm these results.  相似文献   

17.
In vitro whole blood canine assays were used to quantify the inhibitory actions of the novel non-steroidal anti-inflammatory drug (NSAID) robenacoxib on the cyclooxygenase (COX) isoenzymes, COX-1 and COX-2, in comparison with other drugs of the NSAID class. COX-1 activity was determined by measuring serum thromboxane (Tx)B2 synthesis in blood samples allowed to clot at 37 °C for 1 h. COX-2 activity was determined by measuring prostaglandin (PG)E2 synthesis in blood samples incubated at 37 °C for 24 h in the presence of lipopolysaccharide. The rank order of selectivity for inhibition of COX-2 versus COX-1 (IC50 COX-1:IC50 COX-2) for veterinary drugs was highest with robenacoxib (128.8) compared to deracoxib (48.5), nimesulide (29.2), S+ carprofen (17.6), meloxicam (7.3), etodolac (6.6), R? carprofen (5.8) and ketoprofen (0.88). Selectivity expressed as the clinically relevant ratio IC20 COX-1:IC80 COX-2 was highest for robenacoxib (19.8) compared to deracoxib (2.3), S+ carprofen (2.5), R? carprofen (2.1), nimesulide (1.8), etodolac (0.76), meloxicam (0.46) and ketoprofen (0.21).An in vivo pharmacokinetic ex vivo pharmacodynamic study in the dog established dosage and concentration–effect relationships for single oral doses of robenacoxib over the dosage range 0.5–8.0 mg/kg. Values of Cmax and AUC were linearly related to dosage over the tested range. Robenacoxib did not inhibit serum TxB2 synthesis (COX-1) ex vivo at dosages of 0.5–4.0 mg/kg and produced only transient inhibition (at the 1 h and 2 h sampling times) at the 8 mg/kg dosage. All dosages of robenacoxib (0.5–8 mg/kg) produced marked, significant and dose related inhibition of PGE2 synthesis (COX-2) ex vivo.The data demonstrate that in the dog robenacoxib is a highly selective inhibitor of the COX-2 isoform of COX, and significantly inhibits COX-2 and spares COX-1 in vivo when administered orally over the dosage range 0.5–4.0 mg/kg.  相似文献   

18.
ObjectiveTo compare the sedative and clinical effects of intravenous (IV) administration of dexmedetomidine and xylazine in dromedary calves.Study designExperimental, crossover, randomized, blinded study.AnimalsA total of seven healthy male dromedary calves aged 14 ± 2 weeks and weighing 95 ± 5.5 kg.MethodsCalves were assigned three IV treatments: treatment XYL, xylazine (0.2 mg kg−1); treatment DEX, dexmedetomidine (5 μg kg−1); and control treatment, normal saline (0.01 mL kg−1). Sedation scores, heart rate (HR), respiratory rate (fR), rectal temperature (RT) and ruminal motility were recorded before (baseline) and after drug administration. Sedation signs were scored using a 4-point scale. One-way anova and Mann–Whitney U tests were used for data analysis.ResultsCalves in treatments XYL and DEX were sedated at 5–60 minutes. Sedation had waned in XYL calves, but not DEX calves, at 60 minutes (p = 0.037). Sedation was not present in calves of any treatment at 90 minutes. HR decreased from baseline in XYL and DEX at 5–90 minutes after drug administration and was lower in DEX than XYL at 5 minutes (p = 0.017). HR was lower in DEX (p = 0.001) and XYL (p = 0.013) than in control treatment at 90 minutes. fR decreased from baseline in XYL and DEX at 5–60 minutes after drug administration and was lower in DEX than XYL at 5 minutes (p = 0.013). RT was unchanged in any treatment over 120 minutes. Ruminal motility was decreased in XYL at 5, 90 and 120 minutes and absent at 10–60 minutes. Motility was decreased in DEX at 5, 10 and 120 minutes and was absent at 15–90 minutes.Conclusion and clinical relevanceThe duration of sedation from dexmedetomidine (5 μg kg–1) and xylazine (0.2 mg kg–1) was similar in dromedary calves.  相似文献   

19.
The effects of hyoscine-N-butylbromide (hyoscine) and propantheline-bromide (propantheline) on heart rate (HR), HR variability (HRV) and gastrointestinal tract (GIT) contractions in the normal horse were determined. Five adult horses had ECG recordings for 180 min after treatment with propantheline (100 mg), hyoscine (120 mg) or saline. Both propantheline and hyoscine reduced GIT sounds, with propantheline having a longer duration of effect (⩾120 min). Both drugs elevated HR relative to the control baseline period (P < 0.05), with the effects of propantheline again being of longer duration. HRV analysis indicated that propantheline suppressed Total Power (P < 0.05), and both the high frequency (HF) and low frequency (LF) components of the power spectral analysis for up to 60–90 min post treatment. Hyoscine had no effect on HRV Total Power but reduced the HF component for 30 min after drug injection. Time domain variables correlated with Total Power and HF data (P < 0.01). The marked effect of these compounds on parasympathetic control of cardiac and GIT function in normal horses should be taken into consideration when evaluating a clinical response to these agents.  相似文献   

20.
The objective of this study was to establish the clinical pharmacokinetic profile of 4 different opioid drugs (buprenorphine, butorphanol, hydromorphone, and morphine) in the domestic ferret (Mustela putorius furo). Twenty-four, approximately 1-year-old, male neutered purpose-bred domestic ferrets were used for this study. The ferrets were divided into 4 groups of 6, with a different opioid drug used for each group. A preopioid venous blood sample was obtained via cranial vena cava venipuncture. Following the initial blood collection, a single injection of opioid (hydromorphone 0.1 mg/kg, buprenorphine 0.04 mg/kg, butorphanol 0.3 mg/kg, and morphine 1 mg/kg) was given to each ferret, dependent on assigned drug group, intramuscularly (buprenorphine) or subcutaneously (hydromorphone, butorphanol, and morphine). Intramuscular injections were administered in the semimembranosis and semitendinosis muscles, whereas the subcutaneous injections were delivered in the intrascapular subcutaneous space. A venous blood sample was obtained at 5, 15, 30, 60, 120, 240, 360, 480, and 720 minutes postinjection from the ferrets in the buprenorphine, butorphanol, and hydromorphone groups. Mass spectrometry and liquid chromatography was performed to obtain plasma concentrations of the administered drugs. The mean maximum concentration of buprenorphine was 6.96 ng/mL, butorphanol was 48.6 ng/mL, and hydromorphone was 17.3 ng/mL. Maximum concentrations were achieved at a mean of 9 minutes after administration for buprenorphine, 13.3 minutes for butorphanol, and 8.33 minutes for hydromorphone. The mean half-life of buprenorphine was 219.1 minutes, butorphanol was 91.1 minutes, and hydromorphone was 24.7 minutes. Owing to severe complications arising within the morphine group, including hypersalivation and vomiting, the morphine study was discontinued prior to blood sample collection. Intramuscular injections of buprenorphine and subcutaneous injections of butorphanol or hydromorphone appeared to be well tolerated by all ferrets. The pharmacokinetics of buprenorphine, butorphanol, and hydromorphone of a single equipotent dose of each drug have been established through this research investigation and may be useful for further studies.  相似文献   

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