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31.
《Veterinary anaesthesia and analgesia》2020,47(5):705-709
ObjectiveNon-steroidal anti-inflammatory drugs are inhibitors of cyclooxygenase (COX) in tissues and used as therapeutic agents in different species. Grapiprant, a member of the piprant class of compounds, antagonizes prostaglandin receptors. It is a highly selective EP4 prostaglandin E2 receptor inhibitor, thereby limiting the potential for adverse effects caused by wider COX inhibition. The objectives of this study were to determine if the approved canine dose would result in measurable concentrations in horses, and to validate a chromatographic method of analysis for grapiprant in urine and plasma.Study designExperimental study.AnimalsA total of six healthy, adult mixed-breed mares weighing 502 ± 66 (397–600) kg and aged 14.8 ± 5.3 (6–21) years.MethodsMares were administered one dose of 2 mg kg–1 grapiprant via nasogastric tube. Blood and urine samples were collected prior to and up to 48 hours after drug administration. Drug concentrations were measured using high-performance liquid chromatography.ResultsGrapiprant plasma concentrations ranged from 71 to 149 ng mL–1 with the mean peak concentration (106 ng mL–1) occurring at 30 minutes. Concentrations were below the lower limit of quantification (50 ng mL–1) in four of six horses at 1 hour and in all six horses by 2 hours after drug administration. Grapiprant urine concentrations ranged from 40 to 4077 ng mL–1 and were still detectable at 48 hours after administration.Conclusions and clinical relevanceCurrently, there are no published studies looking at the pharmacodynamics of grapiprant in horses. The effective concentration needed to control pain in dogs ranges 114–164 ng mL–1. Oral administration of grapiprant (2 mg kg–1) in horses did not achieve those concentrations. The dose was well tolerated; therefore, studies with larger doses could be conducted. 相似文献
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J. H. Rossmeisl Jr J. L. Robertson K. L. Zimmerman M. A. Higgins D. A. Geiger 《Veterinary and comparative oncology》2009,7(3):173-180
Meningiomas are the most common canine intracranial tumour. Neurologic disability and death from treatment failure remain problematic despite current surgical and radiotheraputic treatments for canine intracranial meningiomas. Cyclooxygenase-2 (COX-2) over-expression has been demonstrated in multiple canine malignancies, and COX-2 inhibitory treatment strategies have been shown to have both preventative and therapeutic effects in spontaneous and experimental models of cancer. The purpose of this study was to evaluate COX-2 expression in canine intracranial meningiomas. Immunohistochemical and Western blot (WB) analyses showed COX-2 expression in multiple tissues of the normal canine brain, and 87% (21/24) of intracranial meningiomas studied were immunoreactive to COX-2. No significant associations between COX-2 immunoreactivity and tumour grade were identified. Further studies are required to elucidate the physiologic roles of constitutive COX-2 expression in the central nervous system as well as its participation in meningioma tumourigenesis. 相似文献
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T.L. Hill B.D.X. Lascelles J. M. Law A.T. Blikslager 《Journal of veterinary internal medicine / American College of Veterinary Internal Medicine》2014,28(3):793-798
Background
Tramadol is a centrally acting analgesic that is often used in conjunction with nonsteroidal anti‐inflammatory drugs (NSAIDs). The effect of coadministration of tramadol and indomethacin on gastric barrier function in dogs is unknown.Hypothesis/Objectives
That coadministration of a nonselective NSAID (indomethacin) and tramadol would decrease recovery of barrier function as compared with acid‐injured, indomethacin‐treated, and tramadol‐treated mucosa.Animals
Gastric mucosa of 10 humanely euthanized shelter dogs.Methods
Ex vivo study. Mounted gastric mucosa was treated with indomethacin, tramadol, or both. Gastric barrier function, prostanoid production, and cyclooxygenase expression were quantified.Results
Indomethacin decreased recovery of transepithelial electrical resistance after injury, although neither tramadol nor the coadministration of the two had an additional effect. Indomethacin inhibited production of gastroprotective prostanoids prostaglandin E2 (acid‐injured PGE 2: 509.3 ± 158.3 pg/mL, indomethacin + acid injury PGE 2: 182.9 ± 93.8 pg/mL, P < .001) and thromboxane B2 (acid‐injured TXB 2: 233.2 ± 90.7 pg/mL, indomethacin + acid injury TXB 2: 37.9 ± 16.8 pg/mL, P < .001), whereas tramadol had no significant effect (PGE 2 P = .713, TXB 2 P = .194). Neither drug had an effect on cyclooxygenase expression (COX‐1 P = .743, COX‐2 P = .705). Acid injury induced moderate to marked epithelial cell sloughing, which was unchanged by drug administration.Conclusions and Clinical Importance
There was no apparent interaction of tramadol and a nonselective cyclooxygenase in this ex vivo model. These results suggest that if there is an adverse interaction of the 2 drugs in vivo, it is unlikely to be via prostanoid inhibition. 相似文献35.
氟尼辛葡甲胺对大鼠小鼠的抗炎镇痛作用研究 总被引:1,自引:2,他引:1
氟尼辛葡甲铵盐是一种动物专用的非甾体抗炎药,具有镇痛和解热功能,但抗炎是其主要功效。本试验通过对鸡蛋清诱导的大鼠踝关节炎性肿胀模型和冰醋酸所致小鼠疼痛扭体反应来研究其抗炎镇痛效果。与对照组相比,FM高中低各剂量组(0.55、1.1、2.2 m g/kg)对大鼠足关节炎症均有显著的对抗作用(P<0.05,P<0.01),呈明显的量效关系。高剂量组(2.2m g/kg)抗炎功效明显优于吲哚美辛组(2.25 m g/kg)和地塞米松组(2.52 m g/kg)。中剂量组(1.1 m g/kg)作用堪比吲哚美辛,而低剂量组(0.55 m g/kg)稍逊于地塞米松。与同类对照药双氯芳酸钠(16.25 m g/kg)和安乃近(32.5 m g/kg)相比,结果显示FM(2.5 m g/kg)对小鼠扭体抑制作用最强,抑制率高达82.69%。 相似文献
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Objective To determine the effects of commonly used ophthalmic corticosteroids, suprofen, polysulfated glycosaminoglycan and preservatives on morphologic characteristics and migration of canine corneal epithelium grown in cell culture. Animals studied Corneal epithelial cells harvested from the corneas of euthanized dogs were propagated in cell culture. Procedures Canine corneal epithelium was grown in tissue culture. The cells were treated with different corticosteroids, polysulfated glycosaminoglycan, suprofen or preservatives at different concentrations after a defect was created in the monolayer. Cellular morphologic characteristics and closure of the defect were compared between test drugs and controls. Results Morphologically the cells treated with dexamethasone were essentially the same as controls. Prednisolone and hydrocortisone caused rounding and shrinkage of the cells. Both suprofen and polysulfated glycosaminoglycan caused no apparent changes in morphologic characteristics at the lowest concentrations tested, but at higher concentrations there was a concentration‐dependent degree of rounding and shrinkage. Benzylkonium chloride and thimerosal caused rounding and shrinkage of all the cells at all concentrations tested. Dexamethasone, hydrocortisone, and suprofen did not inhibit epithelial migration over the defects at the lowest concentrations tested. All other drugs and concentrations inhibited cellular migration. Conclusion Dexamethasone affected the morphologic characteristics and migration of corneal epithelial cells less than hydrocortisone and prednisolone; therefore, dexamethasone may be the drug of choice when a corticosteroid is indicated and an epithelial defect is present. Suprofen and polysulfated glycosaminoglycan caused a concentration‐dependent effect on morphologic characteristics and migration. The preservatives caused severe changes and inhibited migration of the canine corneal epithelial cells at all concentrations and may therefore contribute to poor epithelialization of ulcers treated with preservative‐containing drugs. 相似文献
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A study of the pharmacokinetics and thromboxane inhibitory activity of a single intramuscular dose of carprofen as a means to establish its potential use as an analgesic drug in white rhinoceros
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M. Leiberich R. Krebber M. Hewetson J. Marais V. Naidoo 《Journal of veterinary pharmacology and therapeutics》2018,41(4):605-613
The alleviation of pain and prevention of suffering are key aspects of animal welfare. Unfortunately, analgesic drugs are not available for all species. White rhinoceros (Ceratotherium simum ), representing one of such species, which survive poaching attempts inflicted with severe facial injuries and gunshot wounds, nonetheless require analgesic support. To improve treatment conditions, this study explored the use of carprofen for the treatment of pain and inflammation in white rhinoceros. The pharmacokinetics of 1 mg/kg intramuscular carprofen was evaluated in six healthy white rhinoceros. The half‐life of λz and mean residence time was 105.71 ± 15.67 and 155.01 ± 22.46 hr, respectively. The area under the curve and the maximum carprofen concentration were 904.61 ± 110.78 μg ml?1 hr?1 and 5.77 ± 0.63 μg/ml, respectively. Plasma TXB 2 inhibition demonstrated anti‐inflammatory properties and indicated that carprofen may be effective for a minimum of 48 hr in most animals. With its long half‐life further indicating that a single dose could be effective for several days, we suggest that carprofen may be a useful drug for the treatment of white rhinoceros. 相似文献
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Taylor PM Steagall PV Dixon MJ Ferreira TH Luna SP 《Research in veterinary science》2007,83(3):369-375
A model of nociceptive threshold determination was developed for evaluation of NSAID analgesia in cats. In a crossover study, eight cats received carprofen (4 mg/kg), buprenorphine (0.01 mg/kg) or saline (0.3 ml) subcutaneously before intradermal kaolin injection on the antebrachium to induce mild inflammation. Pressure thresholds were measured at the injected site using blunt-ended pins advanced by manual inflation of a bladder within a bracelet. Bladder pressure was recorded as threshold (PT) at the behavioural end point. Baseline PT were recorded before kaolin injection (time 0). PT was measured at 2-10 h intervals for 52 h. PT below the lower 95% confidence interval (CI) of baseline values indicated hyperalgesia. After saline, hyperalgesia was detected from 2-6 h, 22-26 h, and at 30 and 36 h. After carprofen, PT remained within the 95% CI. After buprenorphine, PT remained within the 95% CI except at 2h. Carprofen and to some extent buprenorphine, prevented inflammatory hyperalgesia. 相似文献
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Effect of topical ophthalmic latanoprost 0.005% solution alone and in combination with diclofenac 0.1% solution in healthy horses: a pilot study
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