mobic and carprofen

Topics: Animals; Carbazoles; Dog Diseases; Dogs; Meloxicam; Osteoarthritis; Randomized Controlled Trials as Topic; Treatment Outcome

Over the past decade, there have been several nonsteroidal anti-inflammatory drugs (NSAIDS) introduced in veterinary medicine with an increased gastrointestinal safety profile consistent with a cyclooxygenase (COX)-1-sparing effect. More recently, an NSAID with additional 5-lipoxygenase (5-LOX) activity has also been approved for use. Although it is tempting to equate in vitro COX-2/COX-1 and 5-LOX inhibition to overall in vivo safety, the data do not support this approach. The true overall safety for any individual compound is based on its evaluation in laboratory margin-of-safety studies, reproductive safety studies, and blind multicenter field studies in client-owned animals. Therefore, when choosing a COX-2-selective or dual-inhibitor NSAID for clinical use, all in vivo data must be taken into account to understand comparative safety, and continued use must be based on the drug's performance in the individual being treated. Until head-to-head trials in multicenter blind studies are published, comments on comparative safety and effectiveness must be reserved.

Topics: 4-Butyrolactone; Animals; Anti-Inflammatory Agents, Non-Steroidal; Carbazoles; Cats; Cyclooxygenase 2 Inhibitors; Dogs; Etodolac; Meloxicam; Pain; Pain Measurement; Pyrazoles; Sulfones; Thiazines; Thiazoles

Most studies of nonsteroidal anti-inflammatory drugs (NSAID) do not demonstrate appreciable differences in efficacy. As awareness of the adverse effects associated with NSAID use increases, safety is becoming the primary concern among physicians when selecting NSAID for use by their human patients. However, veterinarians may be less aware of the safety concerns associated with NSAID use. A wide range of NSAID is used to treat human beings with osteoarthrits; however, it is imperative to remember that dogs are especially sensitive to these drugs, and reports of serious, and occasionally fatal, complications are numerous. Carprofen is a propionic acid-derived NSAID that has anti-inflammatory, analgesic, and antipyretic activity. In animals, carprofen is as potent as indomethacina and more potent than aspirin or phenlbutazone, but carprofen appears to be safer than most other NSAID.

Topics: Acetaminophen; Analgesics, Non-Narcotic; Animals; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Carbazoles; Clonixin; Cyclooxygenase Inhibitors; Dog Diseases; Dogs; Ibuprofen; Indomethacin; Ketoprofen; Meclofenamic Acid; Meloxicam; Naproxen; Osteoarthritis; Pain; Phenylbutazone; Piroxicam; Thiazines; Thiazoles

To compare the effects of meloxicam or carprofen on glomerular filtration rate (GFR), and to evaluate the effect of meloxicam on urinary N-acetyl-β-D-glucosaminidase (NAG) activity, of cats after dental surgery.. Randomized, blinded, controlled trial.. A total of 24 mixed breed cats.. Cats were randomly assigned to one of three groups (n = 8 per group): meloxicam (0.2 mg kg. There was no significant difference in plasma ICL rate (range: from 1.22 ± 0.05 to 1.27 ± 0.04 mL kg minute. Meloxicam and carprofen appeared to produce nonsignificant effects on GFR, and meloxicam did not affect the urinary NAG activity, of cats after dental surgery.

Topics: Acetylglucosaminidase; Animals; Anti-Inflammatory Agents, Non-Steroidal; Carbazoles; Cat Diseases; Cats; Female; Glomerular Filtration Rate; Male; Meloxicam; Tooth Diseases

To evaluate the effects of perioperative oral administration of carprofen and meloxicam on concentrations of 3 acute-phase proteins in dogs undergoing elective ovariohysterectomy (OVH).. 18 healthy adult anestrous female dogs undergoing elective OVH.. Dogs were allocated to 3 groups (6 dogs/group). A placebo treatment, carprofen (2.0 mg/kg), or meloxicam (0.2 mg/kg) was orally administered to the dogs of the respective groups. The initial doses were administered 30 minutes before premedication prior to OVH; additional doses were administered once daily for 4 days after surgery. Blood samples were collected 45 minutes before premedication and 4, 8, 12, 24, 36, 48, 72, 96, and 120 hours after the end of OVH; samples were used for measurement of total WBC and neutrophil counts and concentrations of C-reactive protein (CRP), ceruloplasmin, and fibrinogen.. Values did not differ significantly among groups for WBC and neutrophil counts, serum concentrations of CRP and ceruloplasmin, and plasma concentrations of fibrinogen. Concentrations of all inflammatory markers, except serum ceruloplasmin, increased significantly following OVH, but in a similar manner for each group. No significant changes were detected in serum ceruloplasmin concentrations over time.. Perioperative administration of both carprofen and meloxicam did not significantly affect the concentrations of CRP, ceruloplasmin, and fibrinogen in dogs undergoing OVH. Thus, use of carprofen or meloxicam should not affect clinical interpretation of results for these 3 acute-phase proteins.

Topics: Administration, Oral; Animals; C-Reactive Protein; Carbazoles; Ceruloplasmin; Dogs; Drug Combinations; Enzyme-Linked Immunosorbent Assay; Female; Fibrinogen; Hysterectomy; Leukocyte Count; Meloxicam; Neutrophils; Ovariectomy; Perioperative Care; Statistics, Nonparametric; Thiazines; Thiazoles; Time Factors

Pain associated with poultry lameness is poorly understood. The anti-nociceptive properties of two non-steroidal anti-inflammatory drugs (NSAIDs) were evaluated using threshold testing in combination with an acute inflammatory arthropathy model. Broilers were tested in six groups (n=8 per group). Each group underwent a treatment (saline, meloxicam (3 or 5mg/kg) or carprofen (15 or 25mg/kg)) and a procedure (Induced (arthropathy-induction) or sham (sham-handling)) prior to testing. Induced groups had Freund's complete adjuvant injected intra-articularly into the left intertarsal joint (hock). A ramped thermal stimulus (1°C/s) was applied to the skin of the left metatarsal. Data were analysed using random-intercept multi-level models. Saline-induced birds had a significantly higher skin temperature (± SD) than saline-sham birds (37.6 ± 0.8°C vs. 36.5 ± 0.5°C; Z=-3.47, P<0.001), consistent with an inflammatory response. Saline was associated with significantly lower thermal thresholds (TT) than analgesic treatment (meloxicam: Z=2.72, P=0.007; carprofen: Z=2.58, P=0.010) in induced birds. Saline-induced birds also had significantly lower TT than saline-sham birds (Z=-2.17, P=0.030). This study found direct evidence of an association between inflammatory arthropathies and thermal hyperalgesia, and showed that NSAID treatment maintained baseline thermal sensitivity (via anti-nociception). Quantification of nociceptive responsiveness in a predictable broiler pain model identified thermal anti-hyperalgesic properties of two NSAIDs, which suggested that therapeutically effective treatment was provided at the doses administered. Such validation of analgesic strategies will increase the understanding of pain associated with specific natural broiler lameness types.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthralgia; Carbazoles; Chickens; Hot Temperature; Male; Meloxicam; Nociception; Poultry Diseases; Thiazines; Thiazoles

Leg health of intensively reared broiler chickens is a significant problem, yet little is known regarding the nature of lameness-associated pain. Kinematic changes in gait have been reported in naturally lame broilers following subcutaneous non-steroidal anti-inflammatory drug (NSAID) administration, compared to a placebo group. In the current study, an extensive range of gait parameters were defined using a commercial motion-capturing system to record three-dimensional temporospatial information from walking broilers pre- and post-treatment. Data analysis, performed using multi-level models, revealed gait modifications in broilers receiving NSAID, but not in those receiving saline. The effect of walking velocity was accounted for retrospectively. An increase in velocity following NSAID treatment (carprofen: P<0.001; meloxicam: P=0.044) indicated improved walking ability. For several measures, the polarity of the treatment effect depended upon walking speed. At slow speeds certain parameters become more like those of non-lame broilers, which may have been indicative of improved stability: stride length and duration (both NSAIDs), transverse back displacement (meloxicam), and vertical leg displacement (carprofen). However, these same parameters also revealed that NSAID treatment caused imbalance at faster speeds, which may have signified an excessive dosage. Although doses employed were not conclusively effective, evidence was provided that factors besides body conformation influenced mobility in the test cohort. The study showed that the model would be useful in future studies to increase our understanding of pain associated with specific lameness types in broiler chickens.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Carbazoles; Chickens; Gait; Lameness, Animal; Meloxicam; Poultry Diseases; Thiazines; Thiazoles

To 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.. Randomized, blocked, crossover design with a 14-day washout period.. Healthy intact female Walker Hounds aged 1-6 years and weighing 20.5-24.2 kg.. Dogs 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 B(2) was also measured before and during administration of each drug.. All 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.. Oral 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.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Blood Platelets; Carbazoles; Dogs; Female; Hemostasis; Meloxicam; Platelet Aggregation; Sulfonamides; Thiazines; Thiazoles; Thromboxane B2

One hundred female cats undergoing routine ovariohysterectomy under midazolam-medetomidine-ketamine anaesthesia were included in a blinded, randomised, prospective clinical study to compare postoperative analgesia produced by four analgesic drug combinations given preoperatively (n = 25 per group). A secondary aim was to assess the effects in kittens and pregnant animals. Buprenorphine 180 µg/m(2) or butorphanol 6 mg/m(2) were given with either carprofen 4 mg/kg (groups BUPC and BUTC, respectively) or meloxicam 0.3 mg/kg (groups BUPM or BUTM, respectively). Medetomidine was not antagonised. A simple, descriptive scale (SDS; 0-4), a dynamic and interactive visual analogue scale (DIVAS; 0-100 mm) and mechanical nociceptive thresholds (MT; 2.5-mm diameter probe) were used to evaluate postoperative pain. All pain scores were low (DIVAS <10 mm, SDS <2 and MT >10 N) and there were no significant differences between the groups. It was concluded that all protocols provided adequate analgesia and when used with midazolam-medetomidine-ketamine are effective for routine feline ovariohysterectomy.

Topics: Analgesics, Opioid; Anesthesia, Obstetrical; Anesthetics, Combined; Animals; Behavior, Animal; Buprenorphine; Carbazoles; Cat Diseases; Cats; Double-Blind Method; Female; Humans; Hysterectomy; Meloxicam; Ovariectomy; Pain, Postoperative; Postoperative Care; Pregnancy; Premedication; Prenatal Exposure Delayed Effects; Prospective Studies; Thiazines; Thiazoles; Time Factors; Treatment Outcome

To compare the effects of meloxicam, carprofen, and flunixin meglumine administered IV on the concentration of prostaglandin E(2) (PGE(2)) in the aqueous humor of dogs with aqueocentesis-induced anterior uveitis.. 15 adult dogs with ophthalmically normal eyes.. Each dog was assigned to 1 of 4 treatment groups. Treatment groups were saline (0.9% NaCl) solution (1 mL, IV), meloxicam (0.2 mg/kg, IV), carprofen (4.4 mg/kg, IV), and flunixin meglumine (0.5 mg/kg, IV). Each dog was anesthetized, treatment was administered, and aqueocentesis was performed on each eye at 30 and 60 minutes after treatment. Aqueous humor samples were frozen at -80°C until assayed for PGE(2) concentration with an enzyme immunoassay kit.. For all 4 treatment groups, PGE(2) concentration was significantly higher in samples obtained 60 minutes after treatment, compared with that in samples obtained 30 minutes after treatment, which indicated aqueocentesis-induced PGE(2) synthesis. For aqueous humor samples obtained 60 minutes after treatment, PGE(2) concentration did not differ significantly among groups treated with saline solution, meloxicam, and carprofen; however, the PGE(2) concentration for the group treated with flunixin meglumine was significantly lower than that for each of the other 3 treatment groups.. Flunixin meglumine was more effective than meloxicam or carprofen for minimizing the PGE(2) concentration in the aqueous humor of dogs with experimentally induced uveitis. Flunixin meglumine may be an appropriate pre-medication for use prior to intraocular surgery in dogs.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Aqueous Humor; Carbazoles; Clonixin; Dinoprostone; Dog Diseases; Dogs; Female; Injections, Intravenous; Male; Meloxicam; Thiazines; Thiazoles; Uveitis, Anterior

To compare effects of orally administered tepoxalin, carprofen, and meloxicam for controlling aqueocentesis-induced anterior uveitis in dogs, as determined by measurement of aqueous prostaglandin E(2) (PGE(2)) concentrations.. 38 mixed-breed dogs.. Dogs were allotted to a control group and 3 treatment groups. Dogs in the control group received no medication. Dogs in each of the treatment groups received an NSAID (tepoxalin, 10 mg/kg, PO, q 24 h; carprofen, 2.2 mg/kg, PO, q 12 h; or meloxicam, 0.2 mg/kg, PO, q 24 h) on days 0 and 1. On day 1, dogs were anesthetized and an initial aqueocentesis was performed on both eyes; 1 hour later, a second aqueocentesis was performed. Aqueous samples were frozen at -80 degrees C until assayed for PGE(2) concentrations via an enzyme immunoassay kit.. Significant differences between aqueous PGE(2) concentrations in the first and second samples from the control group indicated that aqueocentesis induced uveitis. Median change in PGE(2) concentrations for the tepoxalin group (10 dogs [16 eyes]) was significantly lower than the median change for the control group (8 dogs [16 eyes]), carprofen group (9 dogs [16 eyes]), or meloxicam group (9 dogs [16 eyes]). Median changes in PGE(2) concentrations for dogs treated with meloxicam or carprofen were lower but not significantly different from changes for control dogs.. Tepoxalin was more effective than carprofen or meloxicam for controlling the production of PGE(2) in dogs with experimentally induced uveitis. Tepoxalin may be an appropriate choice when treating dogs with anterior uveitis.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Carbazoles; Dinoprostone; Dog Diseases; Dogs; Meloxicam; Pyrazoles; Thiazines; Thiazoles; Uveitis, Anterior

Sparing effects of carprofen and meloxicam with or without butorphanol on the minimum alveolar concentration (MAC) of sevoflurane were determined in 6 dogs. Anesthesia was induced and maintained with sevoflurane in oxygen, and MAC was determined by use of a tail clamp method. The dogs were administered a subcutaneous injection of carprofen (4 mg/kg) or meloxicam (0.2 mg/kg), or no medication (control) one hour prior to induction of anesthesia. Following the initial determination of MAC, butorphanol (0.3 mg/kg) was administered intramuscularly, and MAC was determined again. The sevoflurane MACs for carprofen alone (2.10 +/- 0.26%) and meloxicam alone (2.06 +/- 0.20%) were significantly less than the control (2.39 +/- 0.26%). The sevoflurane MACs for the combination of carprofen with butorphanol (1.78 +/- 0.20%) and meloxicam with butorphanol (1.66 +/- 0.29%) were also significantly less than the control value after the administration of butorphanol (2.12 +/- 0.28%). The sevoflurane sparing effects of the combinations of carprofen with butorphanol and meloxicam with butorphanol were additive.

Topics: Administration, Inhalation; Analgesics, Opioid; Anesthesia, Inhalation; Anesthetics, Inhalation; Animals; Anti-Inflammatory Agents, Non-Steroidal; Butorphanol; Carbazoles; Cross-Over Studies; Dogs; Drug Interactions; Drug Therapy, Combination; Meloxicam; Methyl Ethers; Pulmonary Alveoli; Sevoflurane; Thiazines; Thiazoles

To determine the effects of nonsteroidal anti-inflammatory drugs of various cyclooxygenase selectivities on hemostasis and prostaglandin expression in dogs.. 8 client-owned dogs with clinical signs of osteoarthritis.. Dogs received aspirin (5 mg/kg, PO, q 12 h), carprofen (4 mg/kg, PO, q 24 h), deracoxib (2 mg/kg, PO, q 24 h), and meloxicam (0.1 mg/kg, PO, q 24 h) for 10 days each, with an interval of at least 14 days between treatments. On days 0 and 10, blood was collected for platelet aggregation assays, thrombelastography, and measurement of lipopolysaccharide-stimulated prostaglandin E(2), platelet thromboxane B(2) (TXB(2)), and free serum TXB(2) and 6-keto-prostaglandin F (PGF)-1alpha concentrations.. Platelet aggregation decreased after treatment with aspirin and carprofen, whereas significant changes from baseline were not detected for the other drugs tested. Thrombelastograms obtained after treatment with carprofen revealed decreased maximum amplitude and alpha-angle, suggesting hypocoagulability. Maximum amplitude and coagulation index increased after treatment with deracoxib. Plasma concentrations of prostaglandin E(2) decreased after treatment with carprofen or deracoxib, and platelet TXB(2) production increased after treatment with aspirin. Serum concentrations of the prostacyclin metabolite 6-keto-PGF-1alpha did not change significantly after treatment with any of the drugs, although the ratio of free TXB(2) to 6-keto-PGF-1alpha decreased slightly after treatment with carprofen and increased slightly after treatment with deracoxib.. At the dosages tested, treatment with meloxicam affected platelet function minimally in dogs with osteoarthritis. Treatment with carprofen decreased clot strength and platelet aggregation. Clot strength was increased after treatment with deracoxib.

Topics: Animals; Aspirin; Carbazoles; Cross-Over Studies; Cyclooxygenase Inhibitors; Dog Diseases; Dogs; Female; Gene Expression Regulation; Hemostasis; Male; Meloxicam; Osteoarthritis; Platelet Aggregation; Prostaglandins; Sulfonamides; Thiazines; Thiazoles

To evaluate adverse effects of long-term oral administration of carprofen, etodolac, flunixin meglumine, ketoprofen, and meloxicam in dogs.. 36 adult dogs.. 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.. For serum gamma-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.. 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.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Blood Coagulation; Carbazoles; Clonixin; Dog Diseases; Dogs; Etodolac; Female; Ketoprofen; Meloxicam; Stomach Diseases; Thiazines; Thiazoles; Time Factors

This positive-control study evaluated the efficacy of firocoxib versus carprofen, deracoxib, and meloxicam for the prevention of pain and inflammation in a urate crystal synovitis model of lameness. Lameness scoring and force plate gait analysis were used to assess efficacy. The resulting lameness scores and force plate ground reaction forces after urate crystal injection were not significantly different among the groups. Relative to each group's baseline (nonlame) score, only the firocoxib group was not significantly lame, based on lameness score, at the model's peak effect.

Topics: 4-Butyrolactone; Animals; Carbazoles; Cyclooxygenase 2 Inhibitors; Dog Diseases; Dogs; Female; Lameness, Animal; Male; Meloxicam; Severity of Illness Index; Sulfonamides; Sulfones; Synovitis; Thiazines; Thiazoles; Treatment Outcome; Uric Acid

To compare the peri- and post-operative (72 hours) analgesic effects of injectable and orally administered carprofen and meloxicam for ovariohysterectomy in dogs.. Prospective, randomized clinical study.. Forty-three dogs undergoing elective ovariohysterectomy.. Dogs were randomly assigned to receive pre-operative carprofen, meloxicam or sterile saline by subcutaneous injection. Pre-anaesthetic medication was intramuscular acepromazine (0.02 mg kg(-1)) and methadone (0.2 mg kg(-1)). Anaesthesia was induced with either thiopentone or propofol injected to effect, and maintained with isoflurane in oxygen. Visual analogue scores (VAS) for pain and sedation were recorded at 1, 2, 3, 4 and 6 hours following tracheal extubation. Oral medication with the same treatment was continued post-operatively for 3 days, with VAS scores for pain being recorded before, and 2 hours after treatment on each day. Differences between group age, body mass, duration of general anaesthesia, time from treatment injection to tracheal extubation and time from treatment injection to first oral treatment were analysed using one-way analysis of variance and Kruskal-Wallis test. Visual analogue scores for pain and sedation were analysed using a re-randomization method. The significance level was set at p < 0.05.. Meloxicam-treated subjects had lower mean VAS than the control group at 2 and 6 hours following tracheal extubation. Control group VAS were more varied than meloxicam scores (at 6 hours) and carprofen scores (at 3 and 6 hours). On the first post-operative day, pre- to post-treatment VAS scores decreased significantly after meloxicam. On day 3, scores in the meloxicam-treated group were significantly lower than control values after treatment. Changes in pre- to post-treatment VAS were greater in animals receiving either meloxicam or carprofen compared with those given saline.. Both carprofen and meloxicam provided satisfactory analgesia for 72 hours following ovariohysterectomy in dogs.

Topics: Analgesics, Non-Narcotic; Anesthesia; Animals; Carbazoles; Dogs; Female; Hysterectomy; Meloxicam; Ovariectomy; Pain Measurement; Pain, Postoperative; Prospective Studies; Thiazines; Thiazoles; Treatment Outcome

Thirty-two dogs undergoing operations to repair a torn cranial cruciate ligament or a fractured long bone were randomly allocated to one of two treatment groups in a study on postoperative pain. Sixteen of the dogs were given 4 mg/kg carprofen and the other 16 were given 0.2 mg/kg meloxicam subcutaneously before the operation. The signs of pain shown by the animals were assessed for 24 hours on a visual analogue scale, a discontinuous scoring system, and a score based on five behavioural and physiological variables. The dogs' heart and respiratory rates and their mean arterial blood pressures were also measured non-invasively at each assessment. Blood samples were taken before the surgery and 24 hours after it, and the concentrations of urea and creatinine were measured in plasma. Both drugs were effective in relieving the signs of pain for up to 24 hours in all the dogs. There were no significant changes in the concentrations of urea and creatinine, and no adverse effects were reported during the postoperative period.

Topics: Animals; Anterior Cruciate Ligament; Carbazoles; Cyclooxygenase Inhibitors; Dog Diseases; Dogs; Drug Administration Schedule; Female; Fractures, Bone; Male; Meloxicam; Orthopedics; Pain, Postoperative; Thiazines; Thiazoles

The efficacy, tolerance and ease of administration of a nutraceutical, carprofen or meloxicam were evaluated in a prospective, double-blind study on 71 dogs with osteoarthritis. The client-owned dogs were randomly assigned to one of the three treatments or to a placebo control group. The influence of osteoarthritis on the dogs' gait was described by comparing the ground reaction forces of the arthritic dogs and 10 normal dogs. Before the treatments began, and 30 and 60 days later, measurements were made of haematological and biochemical variables and of the ground reaction forces of the arthritic limb, and subjective assessments were made by the owners and by the orthopaedic surgeons. Changes in the ground reaction forces were specific to the arthritic joint, and were significantly improved by carprofen and meloxicam but not by the nutraceutical; the values returned to normal only with meloxicam. The orthopaedic surgeons assessed that there had been an improvement with carprofen and meloxicam, but the owners considered that there had been an improvement only with meloxicam. The blood and faecal analyses did not reveal any changes. The treatments were well tolerated, except for a case of hepatopathy in a dog treated with carprofen.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Ascorbic Acid; Carbazoles; Chondroitin Sulfates; Chronic Disease; Dog Diseases; Dogs; Double-Blind Method; Gait; Glucosamine; Lameness, Animal; Manganese Compounds; Meloxicam; Osteoarthritis; Osteoarthritis, Hip; Osteoarthritis, Knee; Prospective Studies; Severity of Illness Index; Stifle; Thiazines; Thiazoles; Treatment Outcome

Eighty female cats presented for ovariohysterectomy were randomly allocated to one of two treatment groups in this assessor-blinded trial. After pre-anaesthetic assessment, the cats were premedicated with acepromazine (0.1 mg/kg). Anaesthesia was induced with thiopentone and maintained with halothane in oxygen. Forty cats received carprofen (4 mg/kg subcutaneously) and 40 received meloxicam (0.3 mg/kg subcutaneously) after anaesthetic induction. Following routine flank ovariohysterectomy the cats were assessed using visual analogue scale scores for pain and sedation over a 20-hour study period. Blood samples were taken before sedation and at 20 hours for serum biochemistry (urea, creatinine, alanine aminotransferase and aspartate aminotransferase). There were no significant differences between the groups for pain and sedation scores. Serum biochemistry values were similar between the groups, with some differences within groups between the pre-sedation and 20-hour values. One cat in the carprofen group and two cats in the meloxicam group required rescue analgesia with intramuscular morphine (0.2 mg/kg).

Topics: Analgesics, Non-Narcotic; Animals; Anti-Inflammatory Agents, Non-Steroidal; Carbazoles; Cat Diseases; Cats; Female; Hysterectomy; Injections, Subcutaneous; Meloxicam; Ovariectomy; Pain, Postoperative; Thiazines; Thiazoles

The adequacy of postoperative analgesia was assessed in 40 cats following ovariohysterectomy. At extubation, cats were given one dose of carprofen, ketoprofen, meloxicam or tolfenamic acid. Postoperative analgesia was assessed using visual analogue scale (VAS) scoring for pain and sedation; measurement of mechanical nociceptive thresholds at the wound; recognition of the requirement for rescue intervention analgesia; and an overall clinical assessment score at 18 hours. VAS pain scores were low throughout the trial, with no significant differences found between the groups. Postoperative mechanical nociceptive thresholds decreased significantly from baseline in all four groups, with no significant differences between the groups. One cat in each of the tolfenamic acid, ketoprofen and meloxicam groups required rescue intervention analgesia. Nine out of 10 cats in all four groups were classified as having desirable overall clinical assessment scores. In summary, all four drugs provided good postoperative analgesia, although none was able to prevent postoperative wound tenderness.

Topics: Analgesics; Animals; Anti-Inflammatory Agents, Non-Steroidal; Carbazoles; Cats; Female; Hysterectomy; Ketoprofen; Meloxicam; ortho-Aminobenzoates; Ovariectomy; Pain Measurement; Pain, Postoperative; Thiazines; Thiazoles; Treatment Outcome

The nonsteroidal anti-inflammatory drugs meloxicam and carprofen are commonly used as analgesics in mice. The current recommended doses of meloxicam at 0.2-1.0 mg/kg once daily and carprofen at 5-10 mg/kg twice daily may not be adequate to provide analgesia in mice. Several studies have suggested that doses up to 20 mg/kg of meloxicam and carprofen are needed to provide analgesic efficacy. This study investigated the clinical safety of these higher doses of meloxicam and carprofen by evaluating their potential for renal and gastrointestinal toxicity. Female CD-1 mice were given 20 mg/kg of either meloxicam, carprofen, or an equivalent volume of saline subcutaneously once daily for 3 or 7 d. On day 4, mice treated for 3 d were euthanized, and on days 8 and 15, mice treated for 7 d were euthanized. Blood was collected by cardiocentesis for serum chemistry analysis. Feces was collected from the colon for fecal occult blood testing, and tissues were collected for histopathology. No clinically significant changes in serum chemistry profiles were found in the drug-treated mice at any time point as compared with the saline controls. Fecal occult blood and histologic evidence of gastritis was associated with meloxicam administration in mice evaluated at days 4 and 8. By day 15, there was no association with meloxicam treatment and the presence of fecal occult blood or gastritis. There was no association between fecal occult blood and gastritis in the carprofen or saline-treated mice regardless of the treatment durations. These findings suggest that 20 mg/kg of meloxicam in mice causes gastric toxicity when given for 3 or 7 d and should be used cautiously; however, carprofen at 20 mg/kg appears to have minimal toxic effects with regard to the parameters measured.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Carbazoles; Female; Meloxicam; Mice; Thiazines; Thiazoles

In veterinary medicine, the administration of nonsteroidal anti-inflammatory analgesics (NSAIDs) for the control of postsurgical pain in dogs and cats is common given the anti-inflammatory, analgesic, and antipyretic effects of these drugs. This study compared the serum biochemical changes and postoperative analgesic effects of paracetamol, meloxicam, and carprofen in bitches submitted to an ovariohysterectomy using the Dynamic Interactive Visual Analog Scale (DIVAS) and Pain Scale of the University of Melbourne (UMPS) scoring systems.. Thirty bitches of different breeds underwent elective ovariohysterectomies and were randomly assigned to one of three treatment groups: a paracetamol group [15 mg kg-1 intravenous (IV)], a carprofen group (4 mg kg-1 IV), and a meloxicam group (0.2 mg kg-1 IV). All treatments were administered 30 minutes prior to surgery. Paracetamol was administered every 8 hours postoperatively for 48 hours total, while carprofen and meloxicam were intravenously administered every 24 hours. An evaluation of post-surgical pain was done with the DIVAS and the UMPS. The first post-surgical pain measurement was performed 1 hour after surgery and then 2, 4, 6, 8, 12, 16, 20, 24, 36, and 48 hours after surgery.. All groups exhibited a gradual reduction in pain throughout the postoperative period in both scales; however, neither scale significantly differed between the three treatment groups (P > 0.05) during the 48 postoperative hours.. Paracetamol was as effective as meloxicam and carprofen for post-surgical analgesia in bitches subjected to elective ovariohysterectomy. The present study demonstrates that paracetamol may be considered a tool for the effective treatment of acute perioperative pain in dogs. Furthermore, this drug led to no adverse reactions or changes in the parameters assessed in the present study, indicating its safety.

Topics: Acetaminophen; Analgesia; Animals; Anti-Inflammatory Agents, Non-Steroidal; Carbazoles; Cardiorespiratory Fitness; Dogs; Female; Hysterectomy; Kidney Function Tests; Liver Function Tests; Meloxicam; Ovariectomy; Pain, Postoperative

In animal research, authorities require a classification of anticipated pain levels and a perioperative analgesia protocol prior to approval of the experiments. However, data on this topic is rare and so is the reported use of analgesics. We determined surrogate parameters of pain and general well-being after subarachnoid hemorrhage (SAH), as well as the potential for improvement by different systemic analgesia paradigms. Brain injury was induced by filament perforation to mimic SAH. Sham-operated mice were included as surgical control groups with either neck or no-neck preparation. Mice with controlled cortical impact (CCI) injury were included as a control group with traumatic brain injury (TBI), but without neck preparation. Mice were randomized to buprenorphine, carprofen, meloxicam, or vehicle treatment. 24 h after SAH, CCI or sham surgery, pain and stress levels were assessed with a visual assessment score and the amount of food intake was recorded.. Neck preparation, which is required to expose the surgical field for SAH induction, already increased pain/stress levels and sham surgeries for both CCI and SAH reduced food intake. Pain/stress levels were higher and food intake was lower after SAH compared with CCI. Pain/stress levels after CCI without analgesic treatment were similar to levels after SAH sham surgery. Pain treatment with buprenorphine was effective to reduce pain after SAH, whereas lower pain/stress intensity levels after CCI were not improved.. This study emphasizes the importance of pain and stress assessment after surgeries and the efficacy of buprenorphine to improve pain and comfort levels after experimental SAH.

Topics: Animals; Brain Injuries, Traumatic; Buprenorphine; Carbazoles; Eating; Male; Meloxicam; Mice; Pain Measurement; Stress, Psychological; Subarachnoid Hemorrhage

This study investigated the direct effects of non-steroidal anti-inflammatory drugs (NSAIDs) and atrial natriuretic peptide (ANP) on canine-derived vascular endothelial cells (VECs). VECs were isolated and cultured from canine arteries and veins. The mRNA expressions of vascular endothelial growth factor receptor 2, cyclooxygenase-2, and natriuretic peptide receptor 1 were detected in the cultured VECs. The viability of the cultured VECs was reduced in a dose-dependent manner by meloxicam, carprofen, and robenacoxib. By contrast, dose escalations of ANP had only marginal influence on the viability of cultured VECs. NSAIDs may potentially serve as not only analgesic agents against cancerous and perioperative pain but also as adjuvant anti-angiogenic drugs in dogs with malignant tumors.

Topics: Angiogenesis Inhibitors; Animals; Anti-Inflammatory Agents, Non-Steroidal; Atrial Natriuretic Factor; Carbazoles; Cell Survival; Cells, Cultured; Cyclooxygenase 2; Diphenylamine; Dogs; Endothelium, Vascular; Gene Expression; Meloxicam; Phenylacetates; Receptors, Atrial Natriuretic Factor; RNA, Messenger; Vascular Endothelial Growth Factor Receptor-2

Diclofenac, a non-steroidal anti-inflammatory drug (NSAID) was responsible for the death of millions of vultures on the Asian subcontinent, following the consumption of diclofenac contaminated carcasses. The aim of this research was to establish if liver slices could serve as an alternate means of predicting the toxicity of NSAIDs in Gyps vultures. The Cape vulture liver slices was prepared and incubated with four NSAIDs for 6 h. A percent clearance of 1.0 ± 0.253, 0.58 ± 0.153, 0.961 ± 0.312 and 1.242 ± 0.406 (%/h*g) was attained for diclofenac, carprofen, ketoprofen and meloxicam respectively. Both meloxicam and diclofenac exerted toxic effects on the hepatic cells. Protein content indicated that the vulture tissue had lower enzyme levels than expected for an animal of its size. The poor distinction between the ex vivo hepatic percent clearance of meloxicam and diclofenac indicates that liver slices is not an ideal model to investigate NSAIDs toxicity in Cape vulture.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Avian Proteins; Biological Assay; Carbazoles; Diclofenac; Falconiformes; In Vitro Techniques; Ketoprofen; Liver; Male; Meloxicam; Thiazines; Thiazoles

Postoperative analgesia in laboratory rats is complicated by the frequent handling associated with common analgesic dosing requirements. Here, we evaluated sustained-release buprenorphine (Bup-SR), sustained-release meloxicam (Melox-SR), and carprofen gel (CG) as refinements for postoperative analgesia. The aim of this study was to investigate whether postoperative administration of Bup-SR, Melox-SR, or CG effectively controls behavioral mechanical and thermal hypersensitivity in a rat model of incisional pain. Rats were randomly assigned to 1 of 5 treatment groups: saline, 1 mL/kg SC BID; buprenorphine HCl (Bup HCl), 0.05 mg/kg SC BID; Bup-SR, 1.2 mg/kg SC once; Melox-SR, 4 mg/kg SC once; and CG, 2 oz PO daily. Mechanical and thermal hypersensitivity were tested daily from day-1 through 4. Bup HCl and Bup-SR attenuated mechanical and thermal hypersensitivity on days 1 through 4. Melox-SR and CG attenuated mechanical hypersensitivity-but not thermal hypersensitivity-on days 1 through 4. Plasma concentrations, measured by using UPLC with mass spectrometry, were consistent between both buprenorphine formulations. Gross pathologic examination revealed no signs of toxicity in any group. These findings suggest that postoperative administration of Bup HCl and Bup-SR-but not Melox-SR or CG-effectively attenuates mechanical and thermal hypersensitivity in a rat model of incisional pain.

Topics: Analgesics; Animals; Body Weight; Buprenorphine; Carbazoles; Delayed-Action Preparations; Male; Meloxicam; Pain, Postoperative; Random Allocation; Rats; Rats, Sprague-Dawley; Thiazines; Thiazoles

Investigate the effects of administration of meloxicam and carprofen on the mobility of hens with and without keel fractures.. Within each of two experiments a 'blinded' randomised cross over design whereby birds received either the test drug (carprofen or meloxicam) or saline.. Two groups of Lohman Brown hens with and without keel bone fractures.. The first group (n = 63) was treated with carprofen 25 mg kg(-1) and saline subcutaneously, twice. The second group (n = 40) was treated with meloxicam (5 mg kg(-1) ) and saline subcutaneously. The latency of birds to fly down from perches 50, 100 and 150 cm above the ground was measured after each treatment. Data from experiment 1 and 2 were analysed separately; the effects of drug treatment compared with saline on landing time for birds with and without keel bone fractures were evaluated using MLwiN.. In both experiments latency to fly down from perches was longer in hens with keel fractures and there was a significant interaction between perch height and fracture status. For carprofen, at the 50 cm, 100 cm and 150 cm perch heights, birds with fractures took (mean ± SD) 2.5 ± 2.9, 6.8 ± 9.7 and 11.5 ± 13.2 seconds respectively to fly down compared with 1.3 ± 0.5, 2.3 ± 1.2 and 4.2 ± 3.1 seconds for birds without fractures. For meloxicam, at the 50 cm, 100 cm and 150 cm perch heights, birds with fractures took 2.9 ± 2.5, 49.8 ± 85.4 and 100.3 ± 123.6 seconds respectively compared with 0.7 ± 0.5, 2.5 ± 7.1 and 3.0 ± 4.6 seconds to fly down for birds without fractures. There was no significant effect of carprofen or meloxicam treatment.. These data provide further confirmation that keel fractures reduce the willingness of birds to move from perches.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Carbazoles; Chickens; Female; Fractures, Bone; Meloxicam; Motor Activity; Thiazines; Thiazoles

The suppressive effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on the bone healing process have remained controversial, since no clinical data have clearly shown the relationship between NSAIDs and bone healing. The aim of this study was to assess the compensatory response of canine bone marrow-derived mesenchymal stem cells (BMSCs) to several classes of NSAIDs, including carprofen, meloxicam, indomethacin and robenacoxib, on osteogenic differentiation. Each of the NSAIDs (10 µM) was administered during 20 days of the osteogenic process with human recombinant IL-1β (1 ng/ml) as an inflammatory stimulator. Gene expression of osteoblast differentiation markers (alkaline phosphatase and osteocalcin), receptors of PGE2 (EP2 and EP4) and enzymes for prostaglandin (PG) E2 synthesis (COX-1, COX-2, cPGES and mPGES-1) was measured by using quantitative reverse transcription-polymerase chain reaction. Protein production levels of alkaline phosphatase, osteocalcin and PGE2 were quantified using an alkaline phosphatase activity assay, osteocalcin immunoassay and PGE2 immunoassay, respectively. Histologic analysis was performed using alkaline phosphatase staining, von Kossa staining and alizarin red staining. Alkaline phosphatase and calcium deposition were suppressed by all NSAIDs. However, osteocalcin production showed no significant suppression by NSAIDs. Gene expression levels of PGE2-related receptors and enzymes were upregulated during continuous treatment with NSAIDs, while certain channels for PGE2 synthesis were utilized differently depending on the kind of NSAIDs. These data suggest that canine BMSCs have a compensatory mechanism to restore PGE2 synthesis, which would be an intrinsic regulator to maintain differentiation of osteoblasts under NSAID treatment.

Topics: Alkaline Phosphatase; Animals; Anti-Inflammatory Agents, Non-Steroidal; Calcium; Carbazoles; Cell Differentiation; Dinoprostone; Diphenylamine; DNA Primers; Dogs; Gene Expression Profiling; Gene Expression Regulation; Genetic Markers; Immunoassay; Indomethacin; Interleukin-1beta; Meloxicam; Mesenchymal Stem Cells; Osteocalcin; Osteogenesis; Phenylacetates; Statistics, Nonparametric; Thiazines; Thiazoles

Buprenorphine and carprofen, 2 of the most commonly used analgesics in mice, must be administered every 8 to 12 h to provide sustained analgesia. Sustained-release (SR) formulations of analgesics maintain plasma levels that should be sufficient to provide sustained analgesia yet require less frequent dosing and thus less handling of and stress to the animals. The pharmacokinetics of SR formulations of buprenorphine (Bup-SR), butorphanol (Butp-SR), fentanyl (Fent-SR), carprofen (Carp-SR), and meloxicam (Melox-SR) were evaluated in mice over 72 h and compared with those of traditional, nonSR formulations. Bup-SR provided plasma drug levels greater than the therapeutic level for the first 24 to 48 h after administration, but plasma levels of Bup-HCl fell below the therapeutic level by 4 h. Fent-SR maintained plasma levels greater than reported therapeutic levels for 12 h. Therapeutic levels of the remaining drugs are unknown, but Carp-SR provided plasma drug levels similar to those of Carp for the first 24 h after administration, whereas Melox-SR had greater plasma levels than did Melox for the first 8 h. Butp-SR provided detectable plasma drug levels for the first 24 h, with a dramatic decrease over the first 4 h. These results indicate that Bup-SR provides a stable plasma drug level adequate for analgesia for 24 to 48 h after administration, whereas Carp-SR, Melox-SR, Fent-SR, and Butp-SR would require additional doses to provide analgesic plasma levels beyond 24 h in mice.

Topics: Analgesics; Animals; Buprenorphine; Butorphanol; Carbazoles; Delayed-Action Preparations; Female; Meloxicam; Mice; Pain; Thiazines; Thiazoles

We found that carprofen and meloxicam under 3 environmental conditions (ambient dark, ambient light, and 4 °C) remained stable for at least 7 d. We then evaluated the oral pharmacokinetics of meloxicam (20 mg/kg) and carprofen (10 mg/kg) in male C57BL/6 mice after oral gavage or administration in the drinking water. Mice did not drink meloxicam-medicated water but readily consumed carprofen-medicated water, consuming an average of 14.19 mL carprofen-medicated water per 100 g body weight daily; mice drank more during the dark phase than during the light phase. Plasma analyzed by HPLC (meloxicam) and tandem mass spectrometry (carprofen) revealed that the peak meloxicam and carprofen concentrations were 16.7 and 20.3 μg/mL and occurred at 4 and 2 h after oral gavage, respectively. Similar blood levels were achieved after 12 h access to the carprofen-medicated water bottle. At 24 h after oral gavage, the drugs were not detectable in plasma. Meloxicam plasma AUC, elimination half-life, apparent volume of distribution, and apparent oral clearance were 160.4 mg/L × h, 7.4 h, 0.36 L/kg, and 0.125 mL/h × kg, respectively. Carprofen plasma AUC, elimination half-life, apparent volume of distribution, and apparent oral clearance were 160.8 mg/L × h, 7.4 h, 0.42 L/kg, and 0.062 mL/h × kg, respectively. No gross or microscopic evidence of toxicity was seen in any mouse. Our findings indicate that carprofen can be administered in drinking water to mice and that medicated water bottles should be placed 12 to 24 h prior to painful procedures.

Topics: Acute Pain; Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Carbazoles; Chromatography, High Pressure Liquid; Drinking Behavior; Drug Stability; Half-Life; Male; Meloxicam; Mice; Mice, Inbred C57BL; Thiazines; Thiazoles; Water

Cyclooxygenase (COX)-2 participates essentially in bone healing, demonstrated by COX-2 knockout mice that showed delayed fracture repair. Considerable controversy still exists on inhibitory effects of COX-2 inhibitors on bone healing in clinical cases. To assess stage-dependent effects of short-term treatment of COX-2 inhibitors on osteogenic differentiation, a canine POS osteosarcoma cell line which spontaneously differentiates into osteoblastic cell was exposed to COX-2 inhibitors such as carprofen and meloxicam for 72 hours during three different stages of osteoblast differentiation, including day 0 to 3 (pre-osteoblastic stage), day 4 to 7 (transitional stage) and day 8 to 11 (mature osteoblastic stage). As osteogenic markers, expression of alkaline phosphatase (ALP) was estimated by analysis of mRNA expression, enzymatic activity and ALP staining, and expression of osteocalcin was estimated by analysis of mRNA expression after the drug treatments. Calcified matrix formation was finally observed by von Kossa staining on day 14. Expressions of ALP showed no significant suppression by carprofen and meloxicam during all three stages. However, expressions of osteocalcin mRNA and non-calcified nodule formations were delayed by carprofen and meloxicam during transitional stage. Nevertheless, fully calcified nodule formation was observed in all experimental groups during post-medication period. These results indicate that short-term treatment of carprofen and meloxicam would reversibly suppress the differentiation of osteoblasts.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Carbazoles; Cell Differentiation; Cell Line, Tumor; Cyclooxygenase 2; Cyclooxygenase Inhibitors; Dogs; Gene Expression Regulation; Meloxicam; Mice; Mice, Knockout; Osteoblasts; Osteogenesis; Thiazines; Thiazoles

Canine osteoarthritis occurs frequently and causes secondary synovitis. Administration of nonsteroidal anti-inflammatory drugs (NSAIDs) is one of the major therapeutic options for pain management of joint diseases. Tepoxalin has an unique property as an NSAIDs that suppresses both cyclooxygenase and lipoxygenase. The purpose of this study was to evaluate antiproliferative effects of tepoxalin on cultured canine synovial cells. Cytotoxic effects of tepoxalin, carprofen, meloxicam and AA-861 on cultured canine synoviocytes were evaluated by MTT colorimetric assay. Apoptosis was detected by morphological observations with Giemsa or annexin V/Hoechst 33342 staining and by the inhibition of caspase-3 activity with N-Ac-Asp-Glu-Val-Asp-CHO (Ac-DEVD-CHO). Cytotoxic effects of tepoxalin were evident in comparison with the effects of carprofen or meloxicam. The same tendency of cytotoxicity was observed when 5-lipoxygenase was inhibited by AA-861. The morphological findings and contradictory effects of Ac-DEVD-CHO with regard to the cytotoxicity proved the proapoptotic effects of tepoxalin. In conclusion, tepoxalin might control osteoarthritic synovitis by inducing apoptosis in proliferating synoviocytes, while most NSAIDs that selectively inhibit cyclooxygenase-2 most likely would not suppress synovial proliferation.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Apoptosis; Azure Stains; Benzimidazoles; Benzoquinones; Carbazoles; Cells, Cultured; Colorimetry; Cyclooxygenase Inhibitors; Dogs; Fibroblasts; Lipoxygenase Inhibitors; Meloxicam; Pyrazoles; Synovial Fluid; Tetrazolium Salts; Thiazines; Thiazoles

To evaluate the effects of carprofen and meloxicam on conductance and permeability to mannitol and on the histologic appearance of sections of canine gastric mucosa.. Gastric mucosa from 6 mature mixed-breed dogs.. Sections of gastric mucosa were mounted in Ussing chambers, and carprofen (40 or 400μg/mL [CAR40 and CAR400, respectively]), meloxicam (8 or 80μg/mL [MEL8 and MEL80, respectively]), or no drug (controls) was added to the bathing solution. For all sections, conductance was calculated every 15 minutes for 240 minutes and flux of mannitol was calculated for 3 consecutive 1-hour periods; histologic examination was performed after the experiment. The area under the conductance-time curve for each chamber was calculated. Values of conductance × time, flux of mannitol, and the frequency distribution of histologic findings were analyzed for treatment effects.. For CAR400- and MEL80-treated sections, conductance X time was significantly higher than that for control and MEL8-treated sections. The effect of CAR40 treatment was not different from that of any other treatment. Over the three 1-hour periods, mannitol flux increased significantly in MEL80-, CAR40-, and CAR400-treated sections but not in MEL8- treated or control sections. Major histologic changes including epithelial cell sloughing were limited to the CAR400-treated sections.. In the gastric mucosa of dogs, carprofen and meloxicam increased in vitro conductance and permeability to mannitol. At a concentration of 400 μg/mL, carprofen caused sloughing of epithelial cells. Carprofen and meloxicam appear to compromise gastric mucosal integrity and barrier function in dogs.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Carbazoles; Diuretics, Osmotic; Dogs; Gastric Mucosa; Mannitol; Meloxicam; Permeability; Thiazines; Thiazoles

To determine effects of therapeutic dosages of aspirin, carprofen, deracoxib, and meloxicam on platelet function and systemic prostaglandin concentrations in healthy dogs.. 10 hound-crossbred dogs.. Aspirin (10 mg/kg, PO, q 12 h), carprofen (4.4 mg/kg, PO, q 24 h), deracoxib (2 mg/kg, PO, q 24 h), meloxicam (0.1 mg/kg, PO, q 24 h), and a placebo were administered for 7 days in a random order to each of 10 healthy dogs; there was a 21-day washout period between subsequent treatments. One-stage prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen concentration, and plasma concentrations of thromboxane (TX)B(2) and 6-keto prostaglandin (PG)F(1alpha) were measured before and after treatment administration. Platelet function was assessed by use of a platelet-function analyzer and aggregation.. Aspirin, carprofen, and meloxicam did not significantly affect platelet function. Deracoxib caused a mild decrease in platelet aggregation induced by 50microM ADP. Platelet number, Hct, PT, aPTT, and plasma TXB(2) and 6-keto PGF(1alpha) concentrations were unchanged after NSAID administration. Meloxicam administration resulted in a significant decrease in fibrinogen concentration, but results remained within the laboratory reference interval.. Oral administration of commonly used NSAIDs at therapeutic dosages in healthy dogs did not alter plasma TXB(2) and 6-keto PGF(1alpha) concentrations. Deracoxib administration resulted in a minor abnormality in platelet aggregation. Anti-inflammatory doses of aspirin did not affect platelet function as measured by use of optical aggregometry and a platelet-function analyzer. Further evaluation of the effects of aspirin and cyclooxygenase-2-selective inhibitors on hemostasis should be performed.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Blood Coagulation; Blood Platelets; Carbazoles; Dogs; Female; Male; Meloxicam; Ovariectomy; Platelet Aggregation; Prostaglandins; Sulfonamides; Thiazines; Thiazoles

A rapid and new liquid chromatography-mass spectrometry with ion-trap detection method for the determination of meloxicam (MLX), flunixin meglumine (FLU), carprofen (CPF), and tolfenamic acid (TOLF) in animal tissue is described. MRLs between 10 and 500 microg kg(-1) in muscle and between 65 and 1000 microg kg(-1) in liver, from different animal species have been established in the EU for these compounds. After chemical hydrolysis, an organic extraction from homogenised tissue was performed. Final extract was injected in a liquid chromatograph with an ion-trap mass spectrometer with electrospray interface. Four identification points (one precursor and two product ions) and a minimum of one ion ratio was monitored for each compound. For quantitative purposes flunixin-D3 (FLU-D3) was used as internal standard. The method was validated using fortified blank muscle and liver from different animal species according to the 2002/657/EC European decision criteria. The decision limits (CCalpha) and detection capabilities (CCbeta) were determined and their values were at concentrations near the MRL for each substance.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Carbazoles; Cattle; Chemistry Techniques, Analytical; Chromatography, Liquid; Clonixin; Horses; Ions; Liver; Mass Spectrometry; Meloxicam; Muscles; ortho-Aminobenzoates; Swine; Thiazines; Thiazoles

To determine dispersion uniformity and stability of meloxicam and carprofen in extemporaneous preparations stored for 28 days.. Prospective study.. Meloxicam and carprofen (commercial formulations) were compounded (day 0) with deionized water (DW), 1% methylcellulose gel (MCG), MCG and simple syrup (SS; 1:1 mixture), or a suspending and flavoring vehicle combination (SFVC; 1:1 mixture) to nominal drug concentrations of 0.25, 0.5, or 1.0 mg/mL and 1.25, 2.5, or 5.0 mg/mL, respectively.. Preparations were stored at approximately 4 degrees C (39.2 degrees F) or 22 degrees C (71.6 degrees F). For each preparation, drug concentrations were determined and drug stability was evaluated at intervals during storage; on days 0 and 28, pH values were measured and bacterial cultures were initiated.. In meloxicam-DW, meloxicam-MCG (0.25 mg/mL), and meloxicam-MCG (0.5 mg/mL) preparations, drug distribution was uniform (coefficient of variation < 10%); > 90% of the original drug concentration was maintained for 28 days. Despite uniform drug distribution of the carprofen-SFVC preparations, most retained > or = 90% of the original drug concentration for only 21 days. Use of the MCG-SS combination resulted in foamy preparations of unacceptable variability. After 28 days, pH decreased slightly in meloxicam-DW and meloxicam-MCG preparations (0.17 +/- 0.04 and 0.21 +/- 0.04, respectively). Carprofen-SFVC (2.5 mg/mL) and carprofen-MCG-SS (5.0 mg/mL) preparations stored at 22 degrees C for 28 days yielded bacterial growth.. DW, MCG, and the SFVC can be used successfully for extemporaneous preparation of meloxicam and carprofen for administration to small exotic animals. Refrigeration is recommended for preparations of meloxicam-DW and carprofen-SFVC.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Carbazoles; Dose-Response Relationship, Drug; Drug Stability; Drug Storage; Hydrogen-Ion Concentration; Meloxicam; Prospective Studies; Suspensions; Temperature; Thiazines; Thiazoles; Time Factors; Veterinary Drugs

To develop and validate in cats suitable in vitro assays for screening and ranking nonsteroidal antiinflammatory drugs (NSAIDs) on the basis of their inhibitory potencies for cyclooxygenase (COX)-1 and COX-2.. 10 cats.. COX-1 and COX-2 activities in heparinized whole blood samples were induced with calcium ionophore and lipopolysaccharide, respectively. For the COX-2 assay, blood was pretreated with aspirin. The COX-1 and COX-2 assays were standardized, such that time courses of incubation with the test compounds and conditions of COX expression were as similar as possible in the 2 assays. Inhibition of thromboxane B2 production, measured by use of a radioimmunoassay, was taken as a marker of COX-1 and COX-2 activities. These assays were used to test 10 to 12 concentrations of a COX-1 selective drug (SC-560) and of 2 NSAIDs currently used in feline practice, meloxicam and carprofen. Selectivities of these drugs were compared by use of classic 50% and 80% inhibitory concentration (ie, IC50 and IC80) ratios but also with alternative indices that are more clinically relevant.. These assay conditions provide a convenient and robust method for the determination of NSAID selectivity. The S(+) enantiomeric form of carprofen was found to be COX-2 selective in cats, but meloxicam was only slightly preferential for this isoenzyme.. In vitro pharmacodynamic and in vivo pharmacokinetic data predict that the COX-2 selectivity of both drugs for cats will be limited when used at the recommended doses. This study provides new approaches to the selection of COX inhibitors for subsequent clinical testing.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Carbazoles; Cats; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Female; Inhibitory Concentration 50; Male; Meloxicam; Prostaglandin-Endoperoxide Synthases; Pyrazoles; Radioimmunoassay; Thiazines; Thiazoles; Thromboxane B2

We report on the inhibitory activity of the NSAIDs meloxicam, carprofen, phenylbutazone and flunixin, on blood cyclooxygenases in the horse using in vitro enzyme-linked assays. As expected, comparison of IC50 indicated that meloxicam and carprofen are more selective inhibitors of COX-2 than phenylbutazone and flunixin; meloxicam was the most advantageous for horses of four NSAIDs examined. However at IC80, phenylbutazone (+134.4%) and flunixin (+29.7%) had greater COX-2 selectivity than at IC50, and meloxicam (-41.2%) and carprofen (-12.9%) had lower COX-2 selectivity than at IC50. We therefore propose that the selectivity of NSAIDs should be assessed at the 80% as well as 50% inhibition level.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Carbazoles; Clonixin; Cyclooxygenase Inhibitors; Dinoprostone; Female; Horses; In Vitro Techniques; Male; Meloxicam; Phenylbutazone; Thiazines; Thiazoles; Thromboxane B2

A 4-year-old female Siberian Husky was diagnosed with pyogranulomatous steatitis at the site of a recurrence of left anal sac rupture (day 1). Carprofen and orbifloxacin were given for 13 days without improvement. A single dose of meloxicam was administered prior to surgical resection of the anal sac, and based on elevated liver enzyme activity, liver supportive therapy was initiated. The dog received carprofen and orbifloxacin orally on the evening of day 14. The dog became anorectic the following morning, and began vomiting. Despite supportive therapy, the dog was unresponsive to treatment and died on day 16. Postmortem examination revealed severe vacuolar change and acute necrosis of hepatocytes consistent with carprofen and meloxicam induced-toxicosis.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Carbazoles; Chemical and Drug Induced Liver Injury; Dog Diseases; Dogs; Fatal Outcome; Female; Liver; Meloxicam; Steatitis; Thiazines; Thiazoles

Very little is known concerning the occurrence of pain in cancer research models. We wished to establish whether a behaviour-based approach, originally developed to assess postoperative pain, could be used to determine positive effects of the analgesics carprofen and meloxicam in rats that might be experiencing pain during tumour development in an orthotopic model of bladder cancer. An invasive but non-metastatic rat bladder cancer cell line was surgically implanted into the bladder wall of 57 inbred Fisher344 rats. The rats underwent daily clinical assessments. When clinical signs consistent with chronic pain were apparent, behavioural data were collected from 44 animals during 2 x 10 min periods, immediately before and one hour after a subcutaneous injection of either physiological saline (0.9%; 0.2 ml/100 g), carprofen (5 mg/kg) or meloxicam (2 mg/kg). Treatment-associated behaviour changes were then compared between groups. The lack of active behaviour, both before and after each treatment, was consistent with established clinical signs of pain. The rats were so inactive following the treatment that the behavioural technique we had previously developed was of comparatively little use in determining either pain severity or analgesic efficacy. One very prominent effect, however, was an increase in ventral abdominal licking in the control (saline) group. As this was absent in rats given meloxicam or carprofen, and has previously been considered to indicate pain emanating from damaged tissue, it was concluded that the analgesic-treated rats gained at least some benefit from the drug treatments, but it was not possible to gauge the extent of this. Handling for examination or treatment may have intensified pain in rats in the control group, and so this should be avoided whenever possible. It is likely that post-surgical pain differs markedly from cancer pain, so a different set of behavioural markers may be needed to assess it effectively. More intensive behaviour monitoring may help to develop a suitable technique for detecting the onset of, and assess the severity of pain that may occur during tumour development.

Topics: Analysis of Variance; Animals; Behavior, Animal; Carbazoles; Disease Models, Animal; Male; Meloxicam; Pain; Pain Measurement; Pain, Postoperative; Rats; Rats, Inbred F344; Thiazines; Thiazoles; Urinary Bladder Neoplasms

To determine whether administration of the nonsteroidal anti-inflammatory drugs meloxicam or carprofen to healthy dogs that were subsequently anesthetized and subjected to painful electrical stimulation has adverse effects on renal function as measured by glomerular filtration rate (GFR) and evaluation of serum concentrations of urea and creatinine.. 6 male and 6 female healthy young-adult Beagles.. A study was conducted in accordance with a randomized crossover Latin-square design. One of 3 treatments (saline [0.9% NaCl] solution, 0.2 mg of meloxicam/kg, or 4.0 mg of carprofen/kg) was administered i.v. 1 hour before anesthesia was induced by use of drugs in accordance with a standard anesthetic protocol (butorphanol tartrate and acepromazine maleate as preanesthetic medications, ketamine hydrochloride and diazepam for induction, and maintenance with isoflurane). Anesthetized dogs were subjected to intermittent electrical stimulation for 30 minutes. Direct, mean arterial blood pressure; heart rate; and respiratory rate were monitored. End-tidal isoflurane concentration was maintained at 1.5 times the minimum alveolar concentration. The GFR, as measured by plasma clearance of 99mTc-diethylenetriaminepentaacetic acid, and serum concentrations of serum and creatinine were determined 24 hours after induction of anesthesia.. Neither meloxicam nor carprofen significantly affected GFR or serum concentrations of urea and creatinine, compared with values for the saline treatment.. When administered 1 hour before onset of anesthesia and painful electrical stimulation, meloxicam or carprofen did not cause clinically important alterations of renal function in young healthy dogs.

Topics: Anesthesia; Animals; Anti-Inflammatory Agents, Non-Steroidal; Area Under Curve; Blood Pressure; Carbazoles; Creatine; Cross-Over Studies; Dogs; Electric Stimulation; Female; Glomerular Filtration Rate; Heart Rate; Kidney; Male; Meloxicam; Respiration; Thiazines; Thiazoles; Urea

The purpose of this study was to evaluate the effect of the administration of meloxicam; carprofen; and a slow-acting disease modifying osteoarthritis agent, that contains chondroitin sulfate, purified glucosamine, and manganese ascorbate (CS-G-M), on thyroid function in dogs. Forty-six healthy (except for osteoarthritis) euthyroid dogs were blindly assigned to 3 treatment groups: meloxicam, carprofen, and CS-G-M. Each group received the recommended dose of the drug for 60 days. Sixteen other osteoarthritic euthyroid dogs, which received a placebo, were used as a control group to validate the study. For all groups, blood samples were collected on days 0, 30, and 60 to evaluate the serum total and free thyroxine, and endogenous thyrotropin concentrations. There were no significant differences among the treatment groups at each time or within each group over a 60-day period for all parameters. Moreover, none of these values were within the hypothyroid range. Based on the results of this study, the administration of meloxicam, carprofen, and CS-G-M did not affect canine thyroid function evaluation.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Autoantibodies; Carbazoles; Chondroitin Sulfates; Dog Diseases; Dogs; Female; Glucosamine; Longitudinal Studies; Male; Manganese Compounds; Meloxicam; Osteoarthritis; Random Allocation; Thiazines; Thiazoles; Thyroid Function Tests; Thyroid Gland; Thyrotropin; Thyroxine; Treatment Outcome

We have recently demonstrated dose-related analgesic-induced reductions in the occurrence of 7 behavioural activities following midline laparotomy in rats. For these behaviours to be useful in evaluating pain in laboratory rats they must be shown to occur after different types of surgery, and frequently enough to allow rapid scoring of animals. Here, the relevant behaviours were used to test the analgesic efficacy of meloxicam with a variation of our previous laparotomy model. As part of an unrelated project, 57 male Fischer rats were divided into groups to receive either saline (0.2 ml/100g s.c.), meloxicam (0.5, 1 or 2 mg/kg s.c.) or carprofen (2.5, 5, or 10 mg/kg s.c.) 1h before surgery. Behaviour data were collected for 10 min following 25 min of recovery from isoflurane anaesthesia. The cumulative frequencies of back arching, fall/stagger, writhe and poor gait were used to compute a composite behaviour score. Irrespective of whether analyses included only 5 or all 10 min of the observation period, the relevant behaviours occurred significantly more often in rats given saline or low dose meloxicam than in those given 1 or 2 mg/kg of meloxicam, or any dose of carprofen. We conclude that this technique of quantifying post-surgery behaviour is an effective pain scoring method following abdominal surgery in rats, and that 1 mg/kg meloxicam significantly attenuates laparotomy induced pain. Since only a short observation period is required, this approach represents an important practical advance in assessing abdominal pain severity and clinical drug potency.

Topics: Abdominal Pain; Analgesics, Non-Narcotic; Animals; Anti-Inflammatory Agents, Non-Steroidal; Behavior, Animal; Body Weight; Carbazoles; Disease Models, Animal; Exploratory Behavior; Male; Meloxicam; Motor Activity; Pain Measurement; Pain, Postoperative; Rats; Rats, Inbred F344; Thiazines; Thiazoles; Time Factors

Fecal alpha(1)-proteinase inhibitor (alpha(1)-PI) clearance is a reliable, noninvasive marker for protein-losing enteropathy (PLE) in human beings. An assay for measurement of this protein in the dog has been developed and validated and may be useful for the investigation of gastrointestinal disease in this species. Nonsteroidal anti-inflammatory drugs (NSAIDs) frequently are administered to dogs and may have adverse effects on the gastrointestinal tract, including gastroduodenal ulceration and altered mucosal permeability. The value of fecal alpha(1)-PI measurement in detecting unrelated gastrointestinal disease may be limited in dogs on NSAID therapy, but alpha(1)-PI may be a useful marker for NSAID-induced gastrointestinal damage.. The aim of this study was to evaluate the effects of long-term administration of NSAIDs on fecal alpha(1)-PI concentrations in dogs.. Fecal samples were collected from 2 groups of dogs: 1) 21 clinically-healthy client-owned dogs without signs of gastrointestinal disease and receiving no NSAIDs and 2) 7 dogs referred for investigation and treatment of orthopedic disorders; the dogs had received either meloxicam or carprofen daily for at least 30 days. Fecal alpha(1)-PI concentration was measured by ELISA.. Fecal alpha(1)-PI concentrations, expressed as micro g/g of feces, were not significantly different between groups 1 and 2 (median [range], group 1: 9.9 micro g/g [0.0-32.1 micro g/g]; group 2: 5.6 micro g/g [1.1-32.3 micro g/g]; P =.81).. These results suggest that use of cyclooxygenase-2-selective NSAIDs, such as carprofen and meloxicam, does not significantly affect fecal alpha(1)-PI measurements. However, study numbers were small, and larger prospective trials are required to assess more accurately the gastrointestinal effects of NSAIDs in dogs.

Topics: alpha 1-Antitrypsin; Animals; Anti-Inflammatory Agents, Non-Steroidal; Carbazoles; Case-Control Studies; Chronic Disease; Dog Diseases; Dogs; Enzyme-Linked Immunosorbent Assay; Feces; Female; Male; Meloxicam; Protein-Losing Enteropathies; Thiazines; Thiazoles

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.. 12 Beagles and 6 additional Beagles that were used only in serum CRP analyses.. 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.. 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.. 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.

Topics: Acute Disease; Animals; Anti-Inflammatory Agents, Non-Steroidal; Butorphanol; Carbazoles; Dog Diseases; Dogs; Female; Male; Meloxicam; Narcotic Antagonists; Pain; Synovitis; Thiazines; Thiazoles

To evaluate the effects of anti-inflammatory drugs on lipopolysaccharide (LPS)-challenged and -unchallenged equine synovial membrane in terms of production of prostaglandin E2 (PGE2) and hyaluronan, viability, and histomorphologic characteristics.. Synovial membranes were collected from the carpal, tarsocrural, and femoropatellar joints of 6 adult horses.. Synovial membranes from each horse were minced and pooled and explants were treated with one of the following: no drug (control), drug, LPS alone, or LPS and drug. Treatment drugs were phenylbutazone (PBZ), flunixin meglumine (FNX), ketoprofen (KET), carprofen (CRP), meloxicam (MEL), low-concentration methylprednisolone (METH), high-concentration METH, dimethyl sulfoxide (DMSO), or an experimental COX-2 inhibitor (dissolved in DMSO). Following 48 hours of culture, medium was assayed for PGE2 and hyaluronan concentration. Synovial explants were assessed for viability and histomorphologic characteristics.. For the LPS-challenged explants, PBZ, FNX, KTP CRF MEL, and low-concentration METH suppressed PGE2 production, compared with LPS challenge alone. Only MEL suppressed PGE2 production from LPS-challenged explants, compared with unchallenged explants. Synovial explants maintained > 90% viability and there was no significant difference in viability or hyaluronan production among explants. Histomorphologic scores were significantly decreased for explants treated with low-concentration METH or DMSO.. PBZ, FNX, KTP, CRFP MEL, and low-concentration METH suppressed PGE2 production in LPS-challenged explants. Meloxicam appeared to have more selective suppression of COX-2 activity. Histomorphologic scores suggest detrimental effects of METH, DMSO, and the experimental COX-2 inhibitor. Commonly used nonsteroidal anti-inflammatory drugs suppress induced synovial membrane PGE2 production without detrimental effects on synovial membrane viability and function.

Topics: Animals; Anti-Inflammatory Agents; Carbazoles; Clonixin; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Dinoprostone; Horses; Hyaluronic Acid; Isoenzymes; Ketoprofen; Lipopolysaccharides; Meloxicam; Methylprednisolone; Organ Culture Techniques; Phenylbutazone; Prostaglandin-Endoperoxide Synthases; Synovial Membrane; Thiazines; Thiazoles

To establish an in vitro assay and determine the differential suppressive activity of non steroidal anti-inflammatory drugs (NSAID) on cyclooxygenase (COX)-1 and COX-2 isoenzymes in dogs.. COX activity was evaluated in the presence and absence of 4 NSAID (meloxicam, tolfenamic acid, carprofen, and ketoprofen), using a canine monocyte/macrophage cell line that constitutively expresses COX-1, but can be induced to express COX-2 when incubated with lipopolysaccharide. Inhibition of prostaglandin E2 TPGE2) synthesis by each NSAID was measured by enzyme immunoassay and attributed to specific COX-1 or COX-2 activity through assessment of COX messenger RNA expression by use of northern blot analysis and reverse transcription-polymerase chain reaction (RT-PCR). The COX selectivity of each drug was evaluated from dose-response curves by calculating a ratio (COX-1:COX-2) of inhibitory concentration values on the basis of concentrations that reduced PGE2 by 50% in each COX model.. Meloxicam and tolfenamic acid preferentially inhibited COX-2, with meloxicam inhibiting COX-2 activity 12 times more effectively than COX-1 activity. Carprofen was only 1.75 times more selective for COX-2 than for COX-1, and ketoprofen was slightly more selective for COX-1.. COX-1 and COX-2 were differentially sensitive to inhibition in vitro by NSAID. Meloxicam and tolfenamic acid were selective for COX-2. Effects of carprofen and ketoprofen approached equipotency against both isoenzymes. Selective COX-2 inhibitors are a new class of drugs with anti-inflammatory effects similar to conventional NSAID but with fewer adverse effects. Development of these agents for veterinary use would be facilitated by the convenience of using a canine cell line as a model system to screen COX-1 and COX-2 inhibitor activities in vitro.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Blotting, Northern; Carbazoles; Cell Line; Cyclooxygenase Inhibitors; Dinoprostone; DNA; DNA Primers; Dogs; Dose-Response Relationship, Drug; Electrophoresis, Agar Gel; Gene Expression Regulation, Enzymologic; Immunoenzyme Techniques; Isoenzymes; Ketoprofen; Lipopolysaccharides; Meloxicam; ortho-Aminobenzoates; Prostaglandin-Endoperoxide Synthases; Reverse Transcriptase Polymerase Chain Reaction; RNA; Thiazines; Thiazoles

Endoscopy was undertaken to examine the gastroduodenal mucosa of 24 healthy dogs after seven days and again after 28 days of oral non-steroidal anti-inflammatory drug (NSAID) administration. The dogs were divided into four groups. One group received ketoprofen (1 mg/kg every 24 hours), one group carprofen (2 mg/kg every 12 hours for seven days followed by 2 mg/kg every 24 hours), a third group meloxicam suspension (0.2 mg/kg every 24 hours), and the last group gelatin (one capsule every 24 hours). Serum biochemical and complete blood count parameters did not change significantly after NSAID administration. Gastroduodenal lesions were observed in 17 dogs, but in all cases these were mild to moderate. The dogs receiving gelatin or carprofen showed the fewest and the least severe lesions, although there was no statistically significant difference between the three test drugs and the control group (P < or = 0.05). None of the dogs showed any clinical signs related to the gastrointestinal lesions.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Carbazoles; Dogs; Endoscopy, Gastrointestinal; Gastric Mucosa; Gastrointestinal Hemorrhage; Gelatin; Ketoprofen; Meloxicam; Stomach Ulcer; Thiazines; Thiazoles