Safety of reduced-dosage ketoprofen for long-term oral administration in healthy dogs

Tatsuya Narita Department of Clinical Veterinary Science, The United Graduate School of Veterinary Sciences, Gifu University, Gifu, Gifu 501-1193
Department of Small Animal Surgery, Faculty of Agriculture, Iwate University, Morioka, Iwate 020-8550, Japan.

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Reeko Sato Department of Veterinary Internal Medicine, Faculty of Agriculture, Iwate University, Morioka, Iwate 020-8550, Japan.

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Nobuyuki Tomizawa Department of Small Animal Surgery, Faculty of Agriculture, Iwate University, Morioka, Iwate 020-8550, Japan.

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Kenji Tani Department of Small Animal Surgery, Faculty of Agriculture, Iwate University, Morioka, Iwate 020-8550, Japan.

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Shinobu Komori Department of Small Animal Surgery, Faculty of Agriculture, Iwate University, Morioka, Iwate 020-8550, Japan.

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Shigeo Hara Department of Small Animal Surgery, Faculty of Agriculture, Iwate University, Morioka, Iwate 020-8550, Japan.

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Abstract

Objective—To evaluate the safety of reduced-dosage ketoprofen (RDKET) for long-term oral administration in healthy dogs.

Animals—14 healthy Beagles.

Procedures—Racemic ketoprofen (0.25 mg/kg, PO) and gelatin capsules, as a drug-free placebo, were each administered to 7 dogs for 30 days. Dogs were periodically monitored via physical examination, blood analyses, endoscopic examinations, fecal occult blood tests (tetramethylbenzidine and guaiac methods), renal function tests (effective renal plasma flow and glomerular filtration rate), urinalyses, urinary enzyme indices (N-acetyl-β-D-glucosaminidase and γ-glutamyl-transferase), and hemostatic function tests (buccal mucosa bleeding time, cuticle bleeding time, prothrombin time, activated partial thromboplastin time, and fibrinogen concentration).

Results—Pyloric antrum lesion grade was significantly higher in the RDKET group on day 28, compared with the pretreatment and control group grades. Fecal occult blood grade measured by use of the tetramethylbenzidine method was significantly higher in the RDKET group on day 30, compared with the pretreatment grade. No other significant differences were detected between treatment groups.

Conclusions and Clinical Relevance—RDKET induced mild to moderate gastric mucosal injuries especially in the pyloric antrum in healthy Beagles, whereas no adverse effects were observed in renal function or hemostasis. Fecal occult blood tests may be useful as screening tests for adverse gastrointestinal effects induced by RDKET in dogs.

Abstract

Objective—To evaluate the safety of reduced-dosage ketoprofen (RDKET) for long-term oral administration in healthy dogs.

Animals—14 healthy Beagles.

Procedures—Racemic ketoprofen (0.25 mg/kg, PO) and gelatin capsules, as a drug-free placebo, were each administered to 7 dogs for 30 days. Dogs were periodically monitored via physical examination, blood analyses, endoscopic examinations, fecal occult blood tests (tetramethylbenzidine and guaiac methods), renal function tests (effective renal plasma flow and glomerular filtration rate), urinalyses, urinary enzyme indices (N-acetyl-β-D-glucosaminidase and γ-glutamyl-transferase), and hemostatic function tests (buccal mucosa bleeding time, cuticle bleeding time, prothrombin time, activated partial thromboplastin time, and fibrinogen concentration).

Results—Pyloric antrum lesion grade was significantly higher in the RDKET group on day 28, compared with the pretreatment and control group grades. Fecal occult blood grade measured by use of the tetramethylbenzidine method was significantly higher in the RDKET group on day 30, compared with the pretreatment grade. No other significant differences were detected between treatment groups.

Conclusions and Clinical Relevance—RDKET induced mild to moderate gastric mucosal injuries especially in the pyloric antrum in healthy Beagles, whereas no adverse effects were observed in renal function or hemostasis. Fecal occult blood tests may be useful as screening tests for adverse gastrointestinal effects induced by RDKET in dogs.

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