Effects of carprofen administered by different routes to control experimental uveitis in dogs

Estudaram-se os efeitos do carprofeno, aplicado por diferentes vias, em uveítes experimentais em cães. Realizou-se paracentese de câmara anterior em dois momentos (M0 e M1), com intervalo de cinco horas entre si. em M0 e M1, colheram-se 0,2mL de humor aquoso e determinaram-se as concentrações de proteína total e de prostaglandina E2 (PGE2). Constituíram-se quatro grupos (n = 8), que receberam carprofeno ao final de M0 pelas vias subcutânea (GI), subconjuntival (GII) e tópica (GIII). Um quarto grupo não recebeu tratamento (controle). Procedeu-se à avaliação histopatológica nos indivíduos do GII. em todos os grupos, encontrou-se aumento significativo dos níveis proteicos e de PGE2 em M1. Não se observou diferença significativa, em M1, entre os grupos para nenhum dos parâmetros estudados. Exsudado inflamatório de caráter agudo e hemorragia discreta foram vistos à histopatologia após a aplicação do fármaco. O carprofeno foi ineficaz em inibir a síntese de PGE2 e o influxo de proteínas para a câmara anterior, por qualquer uma das vias testadas. Contudo, a redução de 44% nos níveis de proteínas (via tópica), sugere que por esta via ele pode ser utilizado como adjuvante no controle da uveíte em cães.

Analgesia for cats after ovariohysterectomy with either buprenorphine or carprofen alone or in combination

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

Evaluation of the adverse effects of subcutaneous carprofen over six days in healthy cats

This study evaluated the adverse effects of carprofen in seven healthy cats. Values for CBC, biochemical profiles and platelet aggregation were measured before and at seven days after SID treatment with subcutaneous carprofen: 4 mg/kg (day 1), 2 mg/kg (day 2 and 3) and 1 mg/kg (day 4 and 6) (CG) or 0.35 ml of saline (SG) for six days in a randomized, blinded, cross-over study with a four-week washout period. No treatment was given on day 5. Endoscopy of the GI tract was performed pre-treatment and on day 7 post-treatment. There were no significant changes in hematological profiles, biochemical profiles and endoscopy grading scores within nor between groups, except for lower albumin values at baseline than on day 7 (CG), and globulin and ALP values were higher at baseline than on day 7 in CG and SG. SC administration of carprofen over six days did not cause any adverse effects on gastrointestinal, hematological, or serum biochemical variables. (c) 2008 Elsevier Ltd. All rights reserved.

Effects of buprenorphine, carprofen and saline on thermal and mechanical nociceptive thresholds in cats

To evaluate a prototype pressure stimulus device for use in the cat and to compare with a known thermal threshold device.Eight healthy adult cats weighing between 3.0 and 4.9 kg.Pressure stimulation was given via a plastic bracelet taped around the forearm. Three 2.4 mm diameter ball bearings, in a 10-mm triangle, were advanced against the craniolateral surface of the antebrachium by manual 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 also tested. Stimuli were stopped if they reached 55 degrees C or 450 mmHg without response. After four pressure and thermal threshold baselines, each cat received SC buprenorphine 0.01 mg kg(-1), carprofen 4 mg kg(-1) or saline 0.3 mL in a three period cross-over study with a 1-week interval. The investigator was blinded to the treatment. Measurements were made at 0.25. 0.5, 0.75, 1, 2, 3, 4, 6, 8, and 24 hours after injection. Data were analyzed by using ANOVA.There were no significant changes in thermal or pressure threshold after administration of saline or carprofen, but thermal threshold increased from 60 minutes until 8 hours after administration of buprenorphine (p < 0.05). The maximum increase in threshold from baseline (Delta T-max) was 3.5 +/- 3.1 degrees C at 2 hours. Pressure threshold increased 2 hours after administration of buprenorphine (p < 0.05) when the increase in threshold above baseline (Delta P-max) was 162 +/- 189 mmHg.This pressure device resulted in thresholds that were affected by analgesic treatment in a similar manner but to a lesser degree than the thermal method. Pressure stimulation may be a useful additional method for analgesic studies in cats.

Carprofen and buprenorphine prevent hyperalgesia in a model of inflammatory pain in cats

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 2 h. Carprofen and to some extent buprenorphine, prevented inflammatory hyperalgesia. (C) 2007 Elsevier Ltd. All rights reserved.

Evaluation of adverse effects of long-term oral administration of carprofen, etodolac, flunixin meglumine, ketoprofen, and meloxicam in dogs

Objective - To evaluate adverse effects of long-term oral administration of carprofen, etodolac, flunixin meglumine, ketoprofen, and meloxicam in dogs. Animals - 36 adult dogs. Procedures - Values for CBC, urinalysis, serum biochemical urinalyses, and occult blood in feces were investigated before and 7, 30, 60, and 90 days after daily oral administration (n = 6 dogs/group) of lactose (1 mg/kg, control treatment), etodolac (15 mg/kg), meloxicam (0.1 mg/kg), carprofen (4 mg/kg), and ketoprofen (2 mg/kg for 4 days, followed by 1 mg/kg daily thereafter) or flunixin (1 mg/kg for 3 days, with 4-day intervals). Gastroscopy was performed before and after the end of treatment. Results - For serum γ-glutamyltransferase activity, values were significantly increased at day 30 in dogs treated with lactose, etodolac, and meloxicam within groups. Bleeding time was significantly increased in dogs treated with carprofen at 30 and 90 days, compared with baseline. At 7 days, bleeding time was significantly longer in dogs treated with meloxicam, ketoprofen, and flunixin, compared with control dogs. Clotting time increased significantly in all groups except those treated with etodolac. At day 90, clotting time was significantly shorter in flunixin-treated dogs, compared with lactose-treated dogs. Gastric lesions were detected in all dogs treated with etodolac, ketoprofen, and flunixin, and 1 of 6 treated with carprofen. Conclusions and Clinical Relevance - Carprofen induced the lowest frequency of gastrointestinal adverse effects, followed by meloxicam. Monitoring for adverse effects should be considered when nonsteroidal anti-inflammatory drugs are used to treat dogs with chronic pain.

Comparison of analgesic efficacy of preoperative or postoperative carprofen with or without preincisional mepivacaine epidural anesthesia in canine pelvic or femoral fracture repair

OBJECTIVE: To compare analgesic efficacy of preoperative versus postoperative administration of carprofen and to determine, if preincisional mepivacaine epidural anesthesia improves postoperative analgesia in dogs treated with carprofen. STUDY DESIGN: Blind, randomized clinical study. ANIMALS: Dogs with femoral (n=18) or pelvic (27) fractures. METHODS: Dogs were grouped by restricted randomization into 4 groups: group 1 = carprofen (4 mg/kg subcutaneously) immediately before induction of anesthesia, no epidural anesthesia; group 2 = carprofen immediately after extubation, no epidural anesthesia; group 3 = carprofen immediately before induction, mepivacaine epidural block 15 minutes before surgical incision; and group 4 = mepivacaine epidural block 15 minutes before surgical incision, carprofen after extubation. All dogs were administered carprofen (4 mg/kg, subcutaneously, once daily) for 4 days after surgery. Physiologic variables, nociceptive threshold, lameness score, pain, and sedation (numerical rating scale [NRS], visual analog scale [VAS]), plasma glucose and cortisol concentration, renal function, and hemostatic variables were measured preoperatively and at various times after surgery. Dogs with VAS pain scores >30 were administered rescue analgesia. RESULTS: Group 3 and 4 dogs had significantly lower pain scores and amount of rescue analgesia compared with groups 1 and 2. VAS and NRS pain scores were not significantly different among groups 1 and 2 or among groups 3 and 4. There was no treatment effect on renal function and hemostatic variables. CONCLUSIONS: Preoperative carprofen combined with mepivacaine epidural anesthesia had superior postoperative analgesia compared with preoperative carprofen alone. When preoperative epidural anesthesia was performed, preoperative administration of carprofen did not improve postoperative analgesia compared with postoperative administration of carprofen. CLINICAL RELEVANCE: Preoperative administration of systemic opioid agonists in combination with regional anesthesia and postoperative administration of carprofen provides safe and effective pain relieve in canine fracture repair.

Preemptive carprofen for peri-operative analgesia in dogs undergoing Tibial Plateau Leveling Osteotomy (TPLO): a prospective, randomized, blinded, placebo controlled clinical trial

Eighteen client-owned dogs undergoing Tibial Plateau Leveling Osteotomy (TPLO) were included in this blinded clinical study and randomly assigned to one of two treatment groups. Group C (carprofen) received intravenous (IV) carprofen, 4 mg/kg, prior to anesthesia, whereas group P (placebo) received IV saline. General anesthesia was maintained with isoflurane in oxygen and a constant rate infusion (CRI) of sufentanyl IV. Intra-operatively, assessment of nociception was based on changes in physiological parameters and on the analgesics requirement, whereas in the post-operative period evaluation of pain was performed by using a Hellyer and Gaynor pain score and by comparing the doses of rescue buprenorphine required by the two treatment groups. Although no statistically significant differences in intra-operative sufentanyl doses were found between treatment groups, group C had superior cardiovascular stability, and lower post-operative pain scores and rescue buprenorphine doses than group P. Our results indicate that administration of carprofen prior to surgery was effective in improving peri-operative analgesia in dogs undergoing TPLO.

Effect of carprofen, etodolac, meloxicam, or butorphanol in dogs with induced acute synovitis

OBJECTIVE: To compare the analgesic and anti-inflammatory effect of single doses of carprofen, etodolac, meloxicam, and butorphanol in dogs with induced acute synovitis (acute pain model) via kinetic gait analysis and orthopedic evaluation and examine measurement of serum C-reactive protein (CRP) concentration as an indicator of treatment efficacy. ANIMALS: 12 Beagles and 6 additional Beagles that were used only in serum CRP analyses. PROCEDURE: Acute synovitis was induced in right stifle joints of dogs via intra-articular injection of monosodium urate solution. Treatments included butorphanol (0.2 mg/kg, i.v.), carprofen (4 mg/kg, PO), etodolac (17 mg/kg, PO), or meloxicam (0.2 mg/kg, PO); control dogs received no treatment. The procedure was repeated (3-week intervals) until all dogs received all treatments including control treatment. Lameness was assessed on a biomechanical force platform and via orthopedic evaluations of the stifle joints; blood was collected to monitor serum CRP concentration. RESULTS: Compared with control dogs, treated dogs had significantly different vertical ground reaction forces and weight-bearing scores. Greatest improvement in lameness was observed in carprofen-treated dogs. Etodolac had the fastest onset of action. Compared with butorphanol treatment, only carprofen and etodolac were associated with significantly lower pain scores. An increase in serum CRP concentration was detected after intra-articular injection in all dogs; this change was similar among groups. CONCLUSIONS AND CLINICAL RELEVANCE: Carprofen, etodolac, and meloxicam had greater efficacy than butorphanol in relief of acute pain. Carprofen was most effective overall. In this acute pain model, serum CRP analysis was not useful to assess drug efficacy.

Preliminary study on carprofen concentration measurements after transcutaneous treatment with Vetdrop® in a microfracture joint defect model in sheep.

BackgroundThe present preliminary study describes concentration time courses of the NSAID carprofen in the plasma and synovial fluid in a microfrature sheep model after transcutaneous treatments with a novel application device (Vetdrop®). To treat circumscribed inflammatory processes a transcutaneous application device could potentially be beneficial. After transcutaneous application normally lower systemic concentrations are measured which may reduce the incidence of side effects, whereas efficacy is still maintained.In this study carprofen was used based on its capacity to provide analgesia after orthopaedic procedures in sheep and it is considered that it may have a positive influence on the healing of cartilage in low concentrations.ResultsIn all transcutaneously treated animals, carprofen plasma concentrations exceeded those of synovial fluid, although plasma levels remained significantly reduced (300-fold) as compared to carprofen administered intravenously. Furthermore, in contrast to the intravenously treated animals, a modest accumulation of carprofen in plasma and synovial fluid was observed in the transcutaneously treated animals over the 6-week treatment period.ConclusionsThe transcutaneously administered carprofen using the Vetdrop® device penetrated the skin and both, plasma- and synovial concentrations could be measured repeatedly over time. This novel device may be considered a valuable transcutaneous drug delivery system.

Postoperative analgesic effects of intravenous, intramuscular, subcutaneous or oral transmucosal buprenorphine administered to cats undergoing ovariohysterectomy

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

Arthrodesis tarsocrural or tarsometatarsal in 2 dogs using circular external skeletal fixator

An external fixation technique, using a circular fixator, to obtain arthrodesis was evaluated in 2 dogs with infected open lesions and soft tissue damage. In both cases, articular cartilage was curetted, and devitalized bone and necrotic soft tissue were removed. No bone graft was used. The wounds were maintained open and the dogs received postoperative antibiotic therapy. The arthrodesis site was compressed progressively as needed. Infection was eradicated and bony union was obtained in both dogs. It was concluded that the use of a circular fixator is an effective method to achieve arthrodesis.

Efeitos do meloxicam e do carprofeno administrados por diferentes vias no controle da uveíte em cães (Canis familiaris - Linnaeus, 1758)

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)