mobic and tepoxalin

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

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

To evaluate the in vivo effects of firocoxib, meloxicam, and tepoxalin on prostaglandin (PG) and leukotriene production in duodenal mucosa and other target tissues in dogs with chronic osteoarthritis (OA).. 8 dogs with chronic, unilateral OA of the stifle joint.. In a crossover design, each dog received placebo (no treatment), firocoxib, meloxicam, or tepoxalin for 7 days, followed by a 21-day washout period. On the first day of treatment (day 0; baseline) and days 2, 4, and 7, samples of whole blood, synovial fluid, and gastric and duodenal mucosae were collected. Prostaglandin E2 concentrations were measured in synovial fluid of the stifle joint and after ex vivo stimulation of whole blood samples. Synthesis of PGE1 and PGE2 was measured in samples of gastric and duodenal mucosae. Concentrations of thromboxane B2 (TxB2) were measured in whole blood samples. Leukotriene B4 (LTB4) concentrations were measured in samples of whole blood (ex vivo stimulation) and gastric and duodenal mucosae.. Firocoxib, meloxicam, and tepoxalin significantly suppressed whole blood concentrations of PGE2, compared with baseline and placebo concentrations, at days 2, 4, and 7. Tepoxalin significantly suppressed serum TxB2 concentrations, compared with baseline, firocoxib, meloxicam, and placebo, at all 3 time points. Production of PGE1 and PGE2 was significantly lower in duodenal versus gastric mucosa. Tepoxalin significantly decreased rates of PGE1 and PGE2 in duodenal and gastric mucosae, compared with baseline rates.. PG production was lower in the duodenum than in the stomach. Firocoxib had a COX-1-sparing effect in vivo.

Topics: 4-Butyrolactone; Animals; Anti-Inflammatory Agents, Non-Steroidal; Dog Diseases; Dogs; Duodenum; Female; Intestinal Mucosa; Leukotrienes; Male; Meloxicam; Osteoarthritis; Prostaglandins; Pyrazoles; Sulfones; Synovial Fluid; Thiazines; Thiazoles

Medical records where tepoxalin (Zubrin) or meloxicam (Metacam) were prescribed in cats were reviewed and data extracted. Comparisons were performed for exploring changes between pre- and post-non-steroidal anti-inflammatory drug course laboratory tests. Seventy-nine medical records fit the inclusion criteria (n = 57 and n = 22, tepoxalin and meloxicam, respectively). The median dosages administered were 13 and 0.029 mg/kg(/)day (tepoxalin and meloxicam, respectively). Median prescription durations were 11 (2-919) and 93 (4-1814) days for tepoxalin and meloxicam, respectively. Suspected adverse events were reported for tepoxalin (9%, 5/57 cats) and meloxicam (18%, 4/22 cats) a median of 774 and 448 days, respectively, after the prescription started. For cats prescribed meloxicam, there were several statistically significant changes for serum biochemistry and hematology parameters, but median values were within normal limits. These valuable clinical data suggest that tepoxalin and meloxicam are well tolerated in the clinical setting at the doses prescribed in this study.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Cat Diseases; Cats; Female; Male; Meloxicam; Pyrazoles; Retrospective Studies; 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 firocoxib, meloxicam, and tepoxalin administration in healthy cats by measuring the ability of stimulated tissues to synthesize eicosanoids ex vivo.. 8 healthy adult male cats.. In a blinded, randomized, crossover study design, cats were treated with firocoxib (1 mg/kg, PO, q 24 h), meloxicam (0.05 mg/kg, PO, q 24 h), tepoxalin (5.0 mg/kg, PO, q 12 h), or a placebo for 8 days. Blood samples and gastric and duodenal mucosal biopsy specimens were collected on days 0 (baseline; immediately before treatment), 3, and 8 of each treatment period. Thromboxane B2 (TXB2) concentrations were measured in serum, and prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) concentrations were measured in plasma. Prostaglandin E1 (PGE1) synthesis, PGE2 synthesis, and LTB4 concentrations were measured in mucosal biopsy specimens. A 21-day minimum washout period was observed between treatments. Repeated-measures analyses were performed.. Firocoxib and meloxicam administration resulted in a lower plasma PGE2 concentration than at baseline on days 3 and 8 of administration, whereas tepoxalin administration did not. Tepoxalin administration resulted in a lower serum TXB2 concentration and pyloric and duodenal PGE1 synthesis on both days, compared with baseline and placebo administration. Neither firocoxib nor meloxicam administration altered pyloric or duodenal PGE1 synthesis on either day, compared with placebo administration. Tepoxalin administration also resulted in lower pyloric mucosal LTB4 concentrations on both days, compared with baseline values.. Firocoxib and meloxicam administration had no effect on cyclooxygenase-1 activity, whereas tepoxalin administration resulted in inhibition of cyclooxygenase-1 and 5-lipoxygenase.

Topics: 4-Butyrolactone; Animals; Anti-Inflammatory Agents, Non-Steroidal; Cats; Cross-Over Studies; Cyclooxygenase Inhibitors; Dinoprostone; Duodenum; Eicosanoids; Gastric Mucosa; Intestinal Mucosa; Kinetics; Leukotriene B4; Male; Meloxicam; Orchiectomy; Pyrazoles; Reference Values; Sulfones; Thiazines; Thiazoles

To evaluate in vivo effects of tepoxalin, an inhibitor of cyclooxygenase (COX) and lipoxygenase (LOX), on prostaglandin (PG) and leukotriene production in osteoarthritic dogs.. 7 mixed-breed adult dogs with chronic unilateral arthritis of a stifle joint.. Dogs were treated in accordance with a randomized 3-way crossover design. Each dog received an inert substance, meloxicam, or tepoxalin for 10 days. On day 0 (baseline), 3, and 10, dogs were anesthetized and samples of blood, stifle joint synovial fluid, and gastric mucosa were collected. Concentrations of PGE2 were measured in synovial fluid and after lipopolysaccharide stimulation of whole blood; PGE1 and PGE2 synthesis was measured in gastric mucosa. Thromboxane B2 (TxB2) concentration was measured in whole blood. Leukotriene B4 (LTB4) concentration was determined in gastric mucosa and in whole blood after ex vivo stimulation with a calcium ionophore.. Tepoxalin significantly decreased LTB4 concentrations in the blood and gastric mucosa at day 10 and TxB2 concentrations in the blood and PGE2 in the gastric mucosa and synovial fluid at days 3 and 10, compared with baseline values. Meloxicam significantly decreased PGE2 concentrations in the blood at days 3 and 10 and synovial fluid at day 3. Meloxicam also decreased PGE1 and PGE2 synthesis in the gastric mucosa at day 3. Meloxicam did not affect LTB4 synthesis in the blood or LTB4 concentrations in the gastric mucosa.. Tepoxalin has in vivo inhibitory activity against COX-1, COX-2, and 5-LOX in dogs at the current approved recommended dosage.

Topics: Analysis of Variance; Animals; Cross-Over Studies; Cyclooxygenase Inhibitors; Dog Diseases; Dogs; Leukotrienes; Lipoxygenase Inhibitors; Meloxicam; Osteoarthritis; Prostaglandins; Pyrazoles; Thiazines; Thiazoles