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. ABBREVIATIONS NSAID Nonsteroidal anti-inflammatory drug COX Cyclooxygenase PG Prostaglandin TX Thromboxane a. Rimadyl, Pfizer Animal Health, Exton, Pa. b. Deramaxx, Novartis Animal Health, Greensboro, NC. c. Aspirin (low strength, enteric

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in American Journal of Veterinary Research

Abstract

Objective—To evaluate cyclooxygenase (COX) selectivity of several nonsteroidal anti-inflammatory drugs (NSAID) in canine blood in vitro.

Animals—11 healthy adult male hound crosses.

Procedure—9 NSAID were studied at 5 concentrations. Thromboxane B2 (TxB2) was assayed as a measure of COX-1 activity in clotted blood. Prostaglandin E2 (PGE2) was assayed as a measure of COX-2 activity in heparinized, lipopolysaccharide (LPS)-stimulated blood. All assays were competitive ELISA tests. Cyclooxygenase selectivity was expressed as a ratio of the concentration of an NSAID that inhibited 50% of the activity (IC50) of COX-1 to the IC50 of COX-2. A separate ratio of the concentration that inhibited 80% of COX activity (IC80) was also determined. A ratio of < 1.0 indicated selectivity for COX-1, whereas a ratio of > 1.0 indicated COX-2 selectivity.

Results—Ketoprofen, aspirin, and etodolac were COX-1 selective. Piroxicam, meloxicam, and carprofen had COX-2 selectivity. The IC50 and IC80 values were similar for most NSAID.

Conclusion and Clinical Relevance—This methodology provides repeatable data from individual dogs and is comparable to results of previous in vitro and ex vivo models. Findings are also consistent with those of canine studies performed in vivo, suggesting that this is a viable in vitro assessment of the COX selectivity of NSAID in dogs. (Am J Vet Res 2002;63:91–94)

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in American Journal of Veterinary Research

Summary

We attempted to determine the extent to which nonsteroidal anti-inflammatory drugs (NSAID) are used in the treatment of food animals, and whether withdrawal times for milk and slaughter are recommended to clients. A survey questionnaire was mailed to a stratified random sample of 2,000 veterinarians whose practices were at least half food animals. A cross-sectional study was used to examine the responses to determine whether differences existed on the basis of a respondent's geographic location, number of years since graduation from veterinary college, and percentage of practice devoted to beef and dairy cattle.

The response rate was 71% (1,424/2,000). Of those practitioners responding, 93% (1,325/1,424) reported using NSAID, with approximately 57 (751/1,322), 24 (327/1,322), and 18% (244/1,322) of respondents reporting use more than once a week, once a week, and 1 to 2 times per month, respectively. Dairy practitioners reported more frequent use than did beef practitioners. Use of flunixin meglumine was reported more frequently than the use of aspirin, phenylbutazone, or dipyrone. Approximately 88% (1,146/1,306) of respondents that used NSAID did so in combination with antibiotics. Withdrawal times for milk and meat were made on the basis of guidelines for the antibiotic. When using NSAID alone, recommendations for withdrawal times for milk and meat varied extensively. Overall, practitioners indicated that NSAID were useful and necessary for the treatment of food-producing animals.

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in Journal of the American Veterinary Medical Association

. ABBREVIATIONS COX Cyclooxygenase NSAID Nonsteroidal anti-inflammatory drug TXA 2 Thromboxane A 2 PGE 2 Prostaglandin E 2 PGI 2 Prostacyclin PRP Platelet-rich plasma PPP Platelet-poor plasma TXB 2 Thromboxane B 2 LPS Lipopolysaccharide a

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in American Journal of Veterinary Research

. ABBREVIATIONS NSAID Nonsteroidal anti-inflammatory drug COX Cyclooxygenase GIT Gastrointestinal tract a. 21% lab dog diet, Harlan Tekland, Madison, Wis b. Rimadyl sterile injectable solution, Pfizer Animal Health, Paxton, Pa c

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in American Journal of Veterinary Research

Summary

A search of medical records at the Georgia Animal Poison Information Center over a 19-month period revealed 240 cases of dog and cat exposure to nonsteroidal anti-inflammatory drugs (nsaid). The most common nsaid consumed were ibuprofen, acetaminophen, aspirin, and indomethacin. The most common clinical signs of toxicosis were vomiting and diarrhea, cns depression, and circulatory manifestations. Pets are at risk from nsaid toxicosis through administration by the owners or accidental consumption of improperly stored drugs.

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in Journal of the American Veterinary Medical Association

unless a veterinarian could provide justification for its use. ABBREVIATIONS FARAD Food Animal Residue Avoidance Databank NSAID Nonsteroidal anti-inflammatory drug WDI Withdrawal interval FDA-CVM FDA Center for Veterinary Medicine t 1

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in Journal of the American Veterinary Medical Association

SUMMARY

Piroxicam and other nonsteroidal anti-inflammatory drugs (nsaid) have antitumor activity against naturally acquired cancer in dogs and human beings, and against experimentally induced tumors in rodents. We are investigating potential mechanisms of nsaid antitumor activity. The direct cytotoxicity of piroxicam, indomethacin, and aspirin against 4 canine tumor cell lines (transitional cell carcinoma, squamous cell carcinoma, melanoma, and soft tissue sarcoma) was determined in short-term growth rate assays and in clonogenic assays. Piroxicam was evaluated alone and in combination with the lipoxygenase inhibitor zileuton, and in combination with the chemotherapeutic agents cisplatin and carboplatin. The 50% inhibitory concentrations (lC50) against melanoma cells in short-term growth rate assays were: 530 μM piroxicam, 180 μM indomethacin, and greater than 1 mM aspirin. These IC50 values were over 10 times greater than serum concentrations of these drugs that could safely be achieved in vivo. The IC50 of zileuton combined with piroxicam (280 μM) was not different from the IC50 of zileuton alone (230 μM; anova P = 0.47) in melanoma cells. Similarly, addition of piroxicam did not alter the IC50 of either cisplatin (1.6 μM) or carboplatin (6.1 μM). These results suggest that nsaid, at serum concentrations achievable in vivo, do not have direct cytotoxicity against canine tumor cells tested. It is unlikely that the in vivo antitumor activity of nsaid is attributable to a direct cytotoxic effect.

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in American Journal of Veterinary Research

Abstract

Objective—To investigate penetration of a topically applied nonsteroidal anti-inflammatory drug (NSAID) into tissues and synovial fluid.

Animals—5 Greyhounds.

Procedure—Dogs were anesthetized and microdialysis probes placed in the dermis and gluteal muscle over each coxofemoral (hip) joint. Methylsalicylate (MeSA) was applied topically over the left hip joint. Dialysate and plasma (blood samples from the cephalic and femoral veins) were obtained during the subsequent 5 hours. Dogs were euthanatized, and tissue samples and synovial fluid were collected and analyzed for salicylic acid (SA) and MeSA by use of highpressure liquid chromatography.

Results—SA and MeSA concentrations increased rapidly (< 30 minutes after application) in dialysate obtained from treated dermis. Salicylic acid also appeared in plasma within 30 minutes and reached a plateau concentration after 2 hours, although combined drug concentrations (SA plus MeSA) in plasma obtained from femoral vein samples were twice those measured in plasma obtained from the cephalic vein (SA only). Treated muscle had a progressive decrease in NSAID concentration with increasing depth (SA and MeSA), but it was significantly higher than the concentration in untreated muscle. Substantial amounts of SA and MeSA were also measured in synovial fluid of treated joints.

Conclusions and Clinical Relevance—Topically applied NSAIDs can penetrate deeply into tissues and synovial fluid. Local concentrations higher than circulating systemic concentrations are suggestive that direct diffusion and local blood redistribution are contributing to this effect. Systemic blood concentrations may be inadequate to describe regional kinetics of topically applied drugs. (Am J Vet Res 2005;66:1128–1132)

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in American Journal of Veterinary Research

Nonsteroidal anti-inflammatory drugs are highly effective for the treatment of a variety of common diseases in horses, including degenerative joint disease and colic. 1,2 The anti-inflammatory properties of NSAIDs are a result of COX inhibition

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in Journal of the American Veterinary Medical Association