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1.
ObjectiveTo evaluate the cyclooxygenases (COX) inhibition, adverse effects and analgesic efficacy of dipyrone or meloxicam in cats undergoing elective ovariohysterectomy.Study designProspective, blinded, randomized, clinical study.AnimalsA total of 30 healthy young cats.MethodsThe cats were randomly assigned to three postoperative groups: D25 (dipyrone 25 mg kg?1 every 24 hours), D12.5 (dipyrone 12.5 mg kg?1 every 12 hours) and M (meloxicam 0.1 mg kg?1 every 24 hours). In the first 24 hours, the drugs were administered intravenously (IV), and then orally for 6 (dipyrone) or 3 days (meloxicam). Prostanoids thromboxane B2 and prostaglandin E2 concentrations served as indicators of COX activity and, with physiological variables and pain and sedation scores, were measured for 24 hours after first analgesic administration. Rescue analgesia (tramadol, 2 mg kg?1 IV) was provided if Glasgow feline composite measure pain scale (CMPS-Feline) ≥5. Laboratory tests included symmetric dimethylarginine and adverse effects were evaluated regularly up to 7 and 10 days after surgery, respectively. Parametric and nonparametric data were analyzed with two-way anova and Kruskal-Wallis tests, respectively (p < 0.05).ResultsIn the first half hour after analgesic administration, COX-1 activity was close to zero and remained significantly lower than before drug administration for 24 hours in all groups. The inhibition of COX-2 activity was significant for 30 minutes in all groups and up to 4 hours in group M. No alterations in laboratory tests or significant adverse effects were observed. Pain scores and need for rescue analgesia did not differ statistically among groups.ConclusionsDipyrone at both doses and meloxicam provided a nonselective inhibition of COX-1 and -2 activities and effective analgesia without causing significant adverse effects or laboratory tests alterations.Clinical relevanceDipyrone at both doses provides equally effective analgesia without causing adverse effects in cats undergoing ovariohysterectomy.  相似文献   

2.
BACKGROUND: Feline oral squamous cell carcinoma (OSCC) may cause painful bone destruction. Given the local invasiveness and rapid clinical progression of OSCC, conventional therapies are often palliative. In human cancer patients, zoledronate exerts anticancer effects by inhibiting tumor-induced angiogenesis and malignant osteolysis. HYPOTHESIS: Zoledronate will exert in vitro and in vivo anti-angiogenic and antiresorptive effects in feline OSCC. ANIMALS: Eight cats with OSCC were prospectively treated with zoledronate and conventional treatment modalities. METHODS: In vitro, zoledronate's effects in modulating soluble vascular endothelial growth factor (VEGF) secretion and receptor activator of nuclear factor kappaB (NF-kappaB) ligand (RANKL) expression were investigated in a feline OSCC cell line (SCCF1). In vivo, basal serum C-telopeptide (CTx) concentrations were compared among normal and OSCC-bearing cats, and the biologic effects of zoledronate administration in cats with naturally occurring OSCC were quantified by serially assessing circulating serum VEGF and CTx concentrations. RESULTS: In vitro, zoledronate concentrations greater than 3 microM reduce soluble VEGF secretion in the SCCF1 cell line. The expression of RANKL in the SCCF1 cell line was also modulated by zoledronate, with low concentrations (3 microM) decreasing but higher concentrations (30 microM) increasing RANKL expression in comparison with untreated cells. In vivo, cats with bone-invasive OSCC had greater serum CTx concentrations in comparison with geriatric, healthy controls. Treatment with zoledronate rapidly decreased circulating serum VEGF and CTx concentrations in cats with spontaneously occurring OSCC. CONCLUSIONS AND CLINICAL IMPORTANCE: Zoledronate exerts in vitro and in vivo effects that may favor the slowing of tumor growth and pathologic bone turnover associated with OSCC.  相似文献   

3.
Monocarboxylate transporters (MCTs) support tumour growth by regulating the transport of metabolites in the tumour microenvironment. High MCT1 or MCT4 expression is correlated with poor outcomes in human patients with head and neck squamous cell carcinoma (HNSCC). Recently, drugs targeting these transporters have been developed and may prove to be an effective treatment strategy for HNSCC. Feline oral squamous cell carcinoma (OSCC) is an aggressive and treatment‐resistant malignancy resembling advanced or recurrent HNSCC. The goals of this study were to investigate the effects of a previously characterized dual MCT1 and MCT4 inhibitor, MD‐1, in OSCC as a novel treatment approach for feline oral cancer. We also sought to determine the potential of feline OSCC as a large animal model for the further development of MCT inhibitors to treat human HNSCC. In vitro, MD‐1 reduced the viability of feline OSCC and human HNSCC cell lines, altered glycolytic and mitochondrial metabolism and synergized with platinum‐based chemotherapies. While MD‐1 treatment increased lactate concentrations in an HNSCC cell line, the inhibitor failed to alter lactate levels in feline OSCC cells, suggesting an MCT‐independent activity. In vivo, MD‐1 significantly inhibited tumour growth in a subcutaneous xenograft model and prolonged overall survival in an orthotopic model of feline OSCC. Our results show that MD‐1 may be an effective therapy for the treatment of feline oral cancer. Our findings also support the further investigation of feline OSCC as a large animal model to inform the development of MCT inhibitors and future clinical studies in human HNSCC.  相似文献   

4.
ObjectiveTo compare the postoperative analgesic effects of intravenous (IV) lidocaine, meloxicam, and their combination in dogs undergoing ovariohysterectomy.Study designProspective, randomized, double‐blind, controlled clinical trial.AnimalsTwenty‐seven dogs aged (mean ± SD) 16.1 ± 7.5 months and weighing 22.4 ± 17.9 kg scheduled for ovariohysterectomy.MethodsAnaesthesia was induced with propofol and maintained with isoflurane. Dogs (n = 9 in each group) were allocated to receive just prior to and during surgery one of the following regimens: M group, 0.2 mg kg?1 IV meloxicam then a continuous rate infusion (CRI) of lactated Ringer's at 10 mL kg?1 hour?1; L group, a bolus of lidocaine (1 mg kg?1 IV) then a CRI of lidocaine at 0.025 mg kg?1 minute?1; and M + L group, both the above meloxicam and lidocaine treatments. Pain and sedation were scored, and venous samples taken for serum cortisol and glucose measurement before and at intervals for 12 hours after anaesthesia. Pain scores were assessed using a multi‐parameter subjective scoring scale (cumulative scale 0–21) by three observers. The protocol stated that dogs with a total score exceeding 9 or a sub‐score above 3 in any one category would receive rescue analgesia. Sedation was scored on a scale of 0–4.ResultsThere were no significant differences in subjective pain scores, serum cortisol, and glucose concentrations between the three groups. The highest pain score at any time was 5, and no dog required rescue analgesia. None of the three regimens caused any observable side effects during or after anaesthesia. At 1 and 2 hours after extubation dogs in group L were significantly more sedated than in the other two groups.Conclusions and Clinical relevanceThis study suggests that, with the scoring system used, IV lidocaine and meloxicam provide similar and adequate post‐operative analgesia in healthy dogs undergoing ovariohysterectomy.  相似文献   

5.
Meloxicam is a cyclooxygenase (COX) inhibitor with a higher selectivity for cyclooxygenase‐2 (COX‐2) than for cyclooxygenase‐1 (COX‐1). In the laboratory setting, this nonsteroidal anti‐inflammatory drug (NSAID) is commonly selected for analgesia in mice and administered every 24 h. This study characterizes the plasma concentration achieved from a dose of 1.6 mg/kg of meloxicam administered once every 24 h subcutaneously for 72 h in male and female C57BL/6 mice. These values were compared, over time, to reference COX‐2 inhibition constants for meloxicam. No significant differences in trough plasma concentrations were noted between genders. The plasma concentrations were below the COX‐2 IC50 after 12 h. To maintain a plasma concentration at or above the COX‐2 whole blood IC50, the study results suggest an administration frequency of every 12 h when using a dose of 1.6 mg/kg in C57BL/6 mice.  相似文献   

6.
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7.
ObjectiveTo determine effects of anti-inflammatory doses of COX-2 selective NSAIDs carprofen, meloxicam, and deracoxib on platelet function in dogs and urine 11-dehydro-thromboxane B2.Study designRandomized, blocked, crossover design with a 14-day washout period.AnimalsHealthy intact female Walker Hounds aged 1–6 years and weighing 20.5–24.2 kg.MethodsDogs were given NSAIDs for 7 days at recommended doses: carprofen (2.2 mg kg?1, PO, every 12 hours), carprofen (4.4 mg kg?1, PO, every 24 hours), meloxicam (0.2 mg kg?1, PO, on the 1st day then 0.1 mg kg?1, PO, every 24 hours), and deracoxib (2 mg kg?1, PO, every 24 hours). Collagen/epinephrine and collagen/ADP PFA-100 cartridges were used to evaluate platelet function before and during and every other day after administration of each drug. Urine 11-dehydro-thromboxane B2 was also measured before and during administration of each drug.ResultsAll NSAIDs significantly prolonged PFA-100 closure times when measured with collagen/epinephrine cartridges, but not with collagen/ADP cartridges. The average duration from drug cessation until return of closure times (collagen/epinephrine cartridges) to baseline values was 11.6, 10.6, 11 and 10.6 days for carprofen (2.2 mg kg?1 every 12 hours), carprofen (4.4 mg kg?1 every 24 hours), meloxicam and deracoxib, respectively.Conclusions and clinical relevanceOral administration of some COX-2 selective NSAIDs causes detectable alterations in platelet function in dogs. As in humans, PFA-100 collagen/ADP cartridges do not reliably detect COX-mediated platelet dysfunction in dogs. Individual assessment of platelet function is advised when administering these drugs prior to surgery, particularly in the presence of other risk factors for bleeding.  相似文献   

8.
The effect of propolis [it is a water‐soluble derivative (WSDP)] and related polyphenolic compounds of propolis (caffeic acid, caffeic acid phenethyl ester and quercetin), honey, royal jelly and bee venom on tumour growth, metastasizing ability and induction of apoptosis and necrosis in murine tumour models (mammary carcinoma and colon carcinoma) was investigated. WSDP and related polyphenolic compounds showed significant anti‐metastatic effect (P < 0.01 and P < 0.001) given either before or after tumour‐cell inoculation. Oral or systemic application of WSDP or caffeic acid significantly reduced subcutaneous tumour growth and prolonged the survival of mice. Honey also exerted pronounced anti‐metastatic effect (P < 0.05) when applied before tumour‐cell inoculation (peroral 2 g kg?1 for mice or 1 g kg?1 for rats, once a day for 10 consecutive days). Royal jelly did not affect metastasis formation when given intraperitoneally or subcutaneously. However, intravenous administration of royal jelly before tumour‐cell inoculation significantly (P < 0.05) inhibited metastasis formation. When mice were given 105 tumour cells intravenously immediately after bee venom injection, the number of tumour nodules in the lung was significantly lower (P < 0.001) than in untreated mice or mice treated with bee venom subcutaneously. Local presence of bee venom in the tissue caused significant delay in subcutaneous tumour formation. These findings clearly demonstrate that anti‐tumour and anti‐metastatic effects of bee venom are highly dependent on the route of injection and on close contact between components of the bee venom and tumour cells. These data show that honey bee products given orally or systemically may have an important role in the control of tumour growth and tumour metastasizing ability.  相似文献   

9.
Oral squamous cell carcinoma (OSCC) is an aggressive and treatment‐resistant malignancy in both feline and human patients. Recent work has demonstrated aberrant expression of fatty acid synthase (FASN) and an increased capacity for lipogenesis in human OSCC and other cancers. In human OSCC, inhibition of FASN decreased cell viability and growth in vitro, and diminished tumour growth and metastasis in murine preclinical models. This study aimed to characterize FASN as a therapeutic target in feline OSCC. Immunohistochemistry revealed high FASN expression in primary feline OSCC tumours, and FASN expression was detected in OSCC cell lines (3 feline and 3 human) by immunoblotting and quantitative real‐time‐polymerase chain reaction (qRT‐PCR). Orlistat, a FASN inhibitor, substantially reduced cell viability in both feline and human OSCC lines, although feline cell lines consistently displayed higher sensitivity to the drug. FASN mRNA expression among cell lines mirrored sensitivity to orlistat, with feline cell lines expressing higher levels of FASN. Consistent with this observation, diminished sensitivity to orlistat treatment and decreased FASN mRNA expression were observed in feline OSCC cells following incubation under hypoxic conditions. Treatment with orlistat did not potentiate sensitivity to carboplatin in the cell lines investigated; instead, combinations of the 2 drugs resulted in additive to antagonistic effects. Our results suggest that FASN inhibition is a viable therapeutic target for feline OSCC. Furthermore, cats may serve as a spontaneous large animal model for human oral cancer, although differences in the regulation of lipogenesis between these 2 species require further investigation.  相似文献   

10.
Prostaglandin (PG) signalling is involved in human and animal cancer development. PG E2 (PGE2) tumour‐promoting activity has been confirmed and its production is controlled by Cyclooxygenase‐2 (COX‐2) and microsomal PGE synthase‐1 (mPGES‐1). Evidence suggests that mPGES‐1 and COX‐2 contribute to carcinogenesis through the EP2 receptor. The aim of our study was to detect by immunohistochemistry COX‐2, mPGES‐1 and EP2 receptor expression in canine (n = 46) and feline (n = 50) mammary tumours and in mammary non‐neoplastic tissues. COX‐2 positivity was observed in 83% canine and 81% feline mammary carcinomas, mPGES‐1 in 75% canine and 66% feline mammary carcinomas and the EP2 receptor expression was observed in 89% canine and 54% feline carcinomas. The frequency of COX‐2, EP2 receptor and mPGES‐1 expression was significantly higher in carcinomas than in non‐neoplastic tissues and adenomas. COX‐2, mPGES‐1 and EP2 receptor expression was strongly associated. These findings support a role of the COX‐2/PGE2 pathway in the pathogenesis of these tumours.  相似文献   

11.
ObjectiveTo compare the effects of tramadol alone, or in combination with dipyrone or meloxicam, on postoperative pain and analgesia requirement after unilateral mastectomy with or without ovariohysterectomy in dogs.Study designProspective, randomized, clinical study.AnimalsTwenty seven bitches undergoing unilateral mastectomy with or without ovariohysterectomy.MethodsAnesthesia was induced with propofol and maintained with isoflurane and a constant rate infusion of morphine. Before the end of surgery, dogs were randomly assigned to receive intravenous tramadol alone (3 mg kg?1, group T), combined with dipyrone (30 mg kg?1, group TD) or meloxicam (0.2 mg kg?1, group TM). Dogs received additional doses of tramadol (groups T and TM) or tramadol with dipyrone (group TD) at 8 and 16 hours after extubation. Postoperative pain was assessed by a blinded observer before anesthesia (baseline) and at 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours after extubation using a visual analog scale (VAS) and a modified Glasgow scale. Rescue analgesia (morphine, 0.5 mg kg?1) was administered if the Glasgow pain score was >3.5.ResultsThere were no significant differences among groups in pain scores evaluated by the VAS or the Glasgow scale. In groups T, TD and TM, pain scores were significantly higher than at baseline for 6, 8 and 2 hours, respectively. Rescue analgesia was administered to 3/9, 2/9 and 1/9 dogs in groups T, TD and TM, respectively (p > 0.05) [Correction added on 15 August 2013, after first online publication: ‘T, TM and TD’ was changed to ‘T, TD and TM’.].Conclusions and clinical relevanceUnder the conditions of this study, tramadol alone or in combination with dypyrone or meloxicam provided effective analgesia for 24 hours in most dogs after unilateral mastectomy with or without ovariohysterectomy. Further evaluation of combination therapies is needed in larger groups of dogs.  相似文献   

12.
Bisphosphonates (BPs) are a class of non‐hydrolysable analogues of pyrophosphate that have high affinity for bone mineral and are inhibitors of bone resorption. The in vitro effects of two nitrogen‐containing BPs, alendronate (ALE) and zoledronate (ZOL), on growth, induction of apoptosis and effects on cell‐cycle distribution in two canine and two human osteosarcoma (OSA) cell lines are investigated here. Both significantly (P < 0.001) reduced cell growth in all cell lines, as assessed by a colorimetric assay with IC50 values in the range of 7.3–61.4 µM and 7.9–36.3 µM for ALE and ZOL, respectively. Both BPs caused a significant (P < 0.001) dose‐dependent increase in the proportion of cells undergoing apoptosis, as assessed both by cell‐cycle analysis and by annexin‐V binding. Both ALE and ZOL altered the proportion of cells in each phase of the cell cycle, but the extent and proportion was both drug and cell line dependent. These data indicate that the nitrogen‐containing BPs have direct anti‐tumour activity against canine and human OSA cells.  相似文献   

13.
Objective To compare the effects of intravenous (IV) and extradural (ED) methadone on end‐tidal isoflurane concentration (Fe ′ISO) and postoperative analgesic requirements in dogs undergoing femoro‐tibial joint surgery. Study Design Randomized, blinded, clinical study. Animals Twenty‐four healthy client‐owned dogs undergoing surgical repair of ruptured cruciate ligaments. Methods Dogs were randomly assigned to two groups of 12 animals and received either ED or IV methadone (0.3 mg kg?1 diluted with saline to 0.2 mL kg?1). Pre‐anaesthetic medication was IV acepromazine (0.05 mg kg?1). Anaesthesia was induced with propofol and maintained initially with an Fe ′ISO of 1.0% delivered in oxygen. Methadone was injected with the dogs in sternal recumbency; the observer was unaware of the administration route. At 10 minutes (stimulation 1) and 20 minutes (stimulation 2) after methadone administration pelvic limb reflexes were tested by digit‐clamping. The time at skin incision (stimulation 3), joint‐capsule incision (stimulation 4), tibial tuberosity drilling (stimulation 5), fabellar suturing (stimulation 6) and extracapsular tightening (stimulation 7) were noted. Changes in heart rate (HR) and respiratory rate and arterial blood pressure associated with surgery were recorded along with the corresponding Fe ′ISO. After 20 minutes of anaesthesia, Fe ′ISO was decreased to the minimum required to maintain stable anaesthesia. Immediately after tracheal extubation, 1, 2, 3 and 6 hours postoperatively and on the morning after surgery, the degree of pain present was assessed using a numerical rating scale. The HR, respiratory rates and blood pressure were also recorded at these times. Serum cortisol and blood glucose concentrations were measured before pre‐anaesthetic medication and at each postoperative pain scoring interval except at 1 and 2 hours. Ketoprofen (2 mg kg?1), carprofen (4 mg kg?1) or meloxicam (0.2 mg kg?1) were given by subcutaneous injection whenever pain scoring indicated moderate discomfort was present. Results Controlled ventilation was required in six dogs which stopped breathing after IV methadone. The median Fe ′ISO at stimulus 5 was 1.0% in the IV and 0.83% in the ED group. At stimulus 6, Fe ′ISO was 1.0% in the IV and 0.8% in the ED group; the difference was statistically significant (p ≤ 0.05). There was no significant difference in the duration of postoperative analgesia associated with administration route. Conclusions Extradural methadone significantly reduces the isoflurane requirement compared with IV methadone during femoro‐tibial joint surgery in dogs. Clinical relevance Extradural methadone provides safe and effective pain relief in dogs undergoing cruciate ligament repair.  相似文献   

14.
Objective To compare behavioral characteristics of induction and recovery in horses anesthetized with eight anesthetic drug protocols. Study design Randomized prospective experimental study. Animals Eight horses, 5.5 ± 2.4 years (mean ± SD) of age, and weighing 505 ± 31 kg. Methods After xylazine pre‐medication, each of eight horses was anesthetized on four occasions using one of eight different anesthetic induction protocols which incorporated various combinations of ketamine (KET), propofol (PRO), and thiopental (THIO): THIO 8 mg kg?1; THIO 6 mg kg?1 + PRO 0.5 mg kg?1; THIO 4 mg kg?1 + PRO 1 mg kg?1; THIO 2 mg kg?1 + PRO 1.5 mg kg?1; KET 2 mg kg?1; KET 1.5 mg kg?1 + PRO 0.5 mg kg?1; KET 1 mg kg?1 + PRO 1 mg kg?1; KET 0.5 mg kg?1 + PRO 1.5 mg kg?1. Quality of induction and recovery were scored from 1 (poor) to 5 (excellent), and time taken to achieve lateral recumbency, first movement, sternal recumbency, and standing were evaluated. Results Time taken to achieve lateral recumbency after drug administration differed significantly (p < 0.0001) among the various combinations, being shortest in horses receiving THIO‐8 (mean ± SD, 0.5 ± 0.3 minutes) and longest in horses receiving KET‐2 (1.4 ± 0.2 minutes). The best scores for induction quality were associated with KET‐1.5 + PRO‐0.5, and the worst scores for induction quality were associated with KET‐2, although the difference was not significant. Time to first movement varied significantly among drug protocols (p = 0.0133), being shortest in horses receiving KET‐2 (12.7 ± 3.6 minutes) and longest in horses receiving THIO‐8 (29.9 ± 1.5 minutes). Horses receiving THIO‐8 made the greatest number of attempts to attain sternal posture (6.5 ± 4.7) and to stand (1.6 ± 0.8). Horses in the THIO‐8 treatment also received the poorest recovery scores (3.3 ± 1.0 and 3.0 ± 0.7 for sternal and standing postures, respectively). The best recovery scores were associated with combinations comprised mainly of propofol. Conclusions Combining propofol with either ketamine or thiopental modifies behaviors associated with use of the individual drugs. Clinical relevance Quality of early anesthesia recovery in horses may be improved by some combinations of propofol with either thiopental or ketamine.  相似文献   

15.
This study assesses the outcome of two combined treatment strategies for the treatment of feline injection‐site sarcoma (FISS). Twenty‐one cats with primary or recurrent FISS received 3 cycles of neoadjuvant chemotherapy with epirubicin (25 mg m?2), then an anatomical resection of the entire muscle compartment containing the tumour was performed based on the findings of co‐axial imaging. Cats then received a further 3 cycles of adjuvant chemotherapy. Follow‐up was performed by telephone contact with a median follow‐up time of 1072 days. Three cats (14%) developed local tumour recurrence at days 264, 664 and 1573 after surgery. A median survival time could not be calculated as over 80% of the study population remained alive or were censored due to death from other causes. When compared to historical controls, the results of this study demonstrate superior rates of tumour‐free survival and disease‐free interval.  相似文献   

16.
Combination chemotherapy holds promise for improving outcomes in malignancy when compared with single‐agent approaches. Care must be taken to avoid overlapping toxicity and to utilize agents with differing mechanisms of action. A phase I dose‐finding trial was performed to determine the maximally tolerated dose (MTD) of a concurrent toceranib and doxorubicin (DOX) combination protocol where toceranib dose was maintained at or near 2.75 mg kg?1 by mouth every other day (PO EOD) while escalating DOX dosage. The dose‐limiting toxicity was found to be neutropenia and the MTD of the combination was determined to be 25 mg m?2 of DOX q 21 days given concurrently with toceranib 2.75 mg kg?1 PO EOD. This combination was well tolerated with no excessive gastrointestinal toxicity nor novel adverse events (AEs) noted. Anti‐tumour activity was observed in the majority of cases. This combination warrants further investigation in the context of phase II/III clinical trials to characterize efficacy and long‐term AE profiles.  相似文献   

17.
Schmid, V.B., Seewald, W., Lees, P., King, J.N. In vitro and ex vivo inhibition of COX isoforms by robenacoxib in the cat: a comparative study. J. vet. Pharmacol. Therap. 33 , 444–452. Robenacoxib is a novel nonsteroidal anti‐inflammatory drug (NSAID) developed for use in companion animals. Whole blood assays were used to characterize in the cat the pharmacodynamics of robenacoxib for inhibition of the cyclooxygenase (COX) isoforms, COX‐1 and COX‐2, in comparison with other NSAIDs. Based on in vitro IC50COX‐1:IC50COX‐2 ratios, robenacoxib was COX‐2 selective (ratio = 32.2), diclofenac (ratio = 3.9) and meloxicam (ratio = 2.7) were only weakly COX‐2 preferential, and ketoprofen (ratio = 0.049) was COX‐1 selective. In an in vivo pharmacokinetic ex vivo pharmacodynamic study, after both p.o. (1–2 mg/kg) and subcutaneous (2 mg/kg) dosing, robenacoxib achieved peak blood concentrations rapidly (Tmax = 1 h for both administration routes) and was cleared from blood relatively rapidly (mean residence time was 1.70 h after p.o. and 1.79 h after subcutaneous dosing). In ex vivo COX isoform inhibition assays, orally (1–2 mg/kg) or subcutaneously (2 mg/kg) administered robenacoxib significantly inhibited COX‐2, with a relatively short duration of action in the central compartment, and had no effect on COX‐1. Therefore robenacoxib was COX‐2 selective and spared COX‐1 in vivo. In contrast, meloxicam (0.3 mg/kg via subcutaneous injection) inhibited both COX‐1 and COX‐2 isoforms significantly for at least 24 h, indicating nonselectivity in vivo.  相似文献   

18.
Schmid, V. B., Spreng, D. E., Seewald, W., Jung, M., Lees, P., King, J. N. Analgesic and anti‐inflammatory actions of robenacoxib in acute joint inflammation in dog. J. vet. Pharmacol. Therap. 33 , 118–131. The objectives of this study were to establish dose–response and blood concentration–response relationships for robenacoxib, a novel nonsteroidal anti‐inflammatory drug with selectivity for inhibition of the cyclooxygenase (COX)‐2 isoenzyme, in a canine model of synovitis. Acute synovitis of the stifle joint was induced by intra‐articular injection of sodium urate crystals. Robenacoxib (0.25, 0.5, 1.0, 2.0 and 4.0 mg/kg), placebo and meloxicam (0.2 mg/kg) were administered subcutaneously (s.c.) 3 h after the urate crystals. Pharmacodynamic endpoints included data from forceplate analyses, clinical orthopaedic examinations and time course of inhibition of COX‐1 and COX‐2 in ex vivo whole blood assays. Blood was collected for pharmacokinetics. Robenacoxib produced dose‐related improvement in weight‐bearing, pain and swelling as assessed objectively by forceplate analysis (estimated ED50 was 1.23 mg/kg for z peak force) and subjectively by clinical orthopaedic assessments. The analgesic and anti‐inflammatory effects of robenacoxib were significantly superior to placebo (0.25–4 mg/kg robenacoxib) and were non‐inferior to meloxicam (0.5–4 mg/kg robenacoxib). All dosages of robenacoxib produced significant dose‐related inhibition of COX‐2 (estimated ED50 was 0.52 mg/kg) but no inhibition of COX‐1. At a dosage of 1–2 mg/kg administered s.c., robenacoxib should be at least as effective as 0.2 mg/kg of meloxicam in suppressing acute joint pain and inflammation in dogs.  相似文献   

19.
The purpose of this study was to determine the plasma pharmacokinetics (PK) and toxicity of zebularine, an oral cytidine analog with demethylating activity, in dogs. Plasma zebularine concentrations were determined by HPLC‐MS/MS following an oral zebularine dose of 8 or 4 mg kg?1. Plasma zebularine clearance was constant. Mean maximum concentration (Cmax) was 23 ± 4.8 and 8.6 ± 1.4 µM following 8 and 4 mg kg?1, respectively. Mean half‐life was 5.7 ± 0.84 and 7.1 ± 2.1 following 8 and 4 mg kg?1, respectively. A single 8 mg kg?1 dose was well tolerated. Daily 4 mg kg?1 treatment in three laboratory dogs resulted in grade 4 neutropenia (n = 3), grade 1 anorexia (n = 2) and grade 1 or 2 dermatologic changes (n = 2). All adverse events resolved with supportive care. A 4 mg kg?1 dose every 21 days was well tolerated. A follow‐up dose escalation study is in progress with a lower starting dose.  相似文献   

20.
NSAID s are often used in horses with colic syndrome during the postoperative period, due to their ability to contrast endotoxemia and to promote an analgesic and anti‐inflammatory effect. As the pharmacokinetics of a drug are often modified in unhealthy animals compared to healthy subjects, the aim of this study was to evaluate the pharmacokinetic profile of meloxicam after i.v. administration in horses undergoing laparotomy for colic syndrome. Eight horses received 0.6 mg/kg of meloxicam i.v. towards the end of surgery. Blood samples were taken at scheduled time points during the following 24 hr. The serum concentration of the drug was determined by HPLC . Terminal half‐life (6.88 ± 2.96 hr), volume of distribution at steady‐state (186.53 ± 61.20 ml/Kg) and clearance (27.91 ± 5.72 ml kg?1 hr?1) were similar to those reported in literature for healthy horses. This result suggests that no adjustment of the approved dose should be necessary when meloxicam is used to treat horses in the immediate postoperative period after surgery for colic syndrome.  相似文献   

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