876 Scientific Reports: Original Study JAVMA, Vol 228, No. 6, March 15, 2006 SMALL ANIMALS C arprofen is a widely used medication prescribed to alleviate chronic pain in dogs. 1-3 Although all NSAIDs have the potential for causing gastrointestinal, renal, and hepatic problems, carprofen is generally considered to be well tolerated by dogs. 1-5 In several studies, 6-8 the drug was not found to induce substantial lesions in the gastric mucosa of dogs, and when admin- istration of carprofen is combined with general anes- thesia in healthy dogs, reported effects on renal func- tion have typically been minor, 9-12 with only a few investigators reporting decreased function. 13 However, severe adverse effects associated with carprofen admin- istration, including hepatocellular toxicosis 14 and neu- trophilic dermatitis with immune-mediated anemia and thrombocytopenia, 15 have been described. Clinical and experimental studies 9-13 on the adverse effects of carprofen have concentrated on dogs in the perioperative and perianesthetic periods. In clinical tri- als of treatment of chronic pain and in tolerance stud- ies, 1,2,4,8 treatment or follow-up periods have typically not extended beyond 2 weeks. The number of clinical or experimental reports 3,5,7 in which adverse effects of carprofen were evaluated after administration for sev- eral weeks or months is limited. To our knowledge, no placebo-controlled clinical trials on the adverse effects of long-term carprofen administration in dogs have been published. The aim of the present study was to evaluate potential adverse effects, especially those involving the kidneys and liver, of a 2-month course of orally admin- istered carprofen in dogs. Our hypothesis was that long-term administration would alter certain blood or urine biochemical variables and cause clinically detectable adverse effects. Materials and Methods Dogs—Twenty-two dogs with clinical signs and a radiographic diagnosis of chronic osteoarthritis in 1 or both hip or elbow joints were included. Mean ± SD weight was 36.5 ± 8.4 kg (80.3 ± 18.5 lb), and mean age was 5.7 ± 2.5 years (range, 1 to 11 years). Ten of the dogs were female, and 12 were male. Seven were German Shepherd Dogs, and the rest represented 10 other breeds. Samples for this study were collected as part of a larger study a in which the efficacies of different treatments for chron- ic orthopedic pain were compared. Owners were instructed to refrain from administering NSAIDs or cortico-steroids for at least 30 days and sodium pentosan polysulfate for at least 90 days prior to the initiation of the study (as inclusion criteria for the efficacy study a ). During the present trial, no medications other than routine vaccinations and antiparasitic treatments were allowed. However, for ethical reasons, at the beginning of the trial, owners were supplied with a supplementary package of carprofen b in normal packaging to be used as additional pain relief (dosage: 1 tablet [50 mg] once daily for dogs weighing 20 to 30 kg [44 to 66 lb], 2 tablets for dogs weighing 31 to 40 kg [68 to 88 lb], and 3 tablets for dogs weighing 41 to 60 kg [90 to 132 lb]) if the owner judged the dog to be in considerable pain. Use of extra carprofen was recorded by the owner. Dogs Evaluation of adverse effects of long-term orally administered carprofen in dogs Marja R. Raekallio, DVM, PhD; Anna K. Hielm-Björkman, DVM; Johanna Kejonen, DVM; Hanna M. Salonen, DVM; Satu M. Sankari, DVM, PhD Objective—To evaluate the adverse effects of carpro- fen in dogs after oral administration for 2 months. Design—Prospective, randomized, blinded, placebo- controlled clinical trial. Animals—22 dogs with osteoarthritis in the hip or elbow joint. Procedure—13 dogs received orally administered carprofen daily for 2 months, and 9 dogs received a placebo for 2 months. Dogs were weighed, and serum and urine samples were collected before initi- ation of treatment and 4 and 8 weeks after initiation of treatment. Serum concentrations of total protein, albumin, urea, and creatinine and serum activities of alkaline phosphatase (ALP) and alanine aminotrans- ferase (ALT) were measured. Urinary ALP-to-creati- nine, γ-glutamyltransferase (GGT)-to-creatinine, and protein-to-creatinine ratios were calculated. Dogs were observed by owners for adverse effects. Results—Serum protein and albumin concentrations were lower in treated dogs than in those that received placebo at 4 weeks, but not at 8 weeks. No changes were observed in serum urea or creatinine concen- trations; ALP or ALT activity; or urinary ALP-to-creati- nine, GGT-to-creatinine, or protein-to-creatinine ratios. Dogs’ weights did not change. Severity of vomiting, diarrhea, and skin reactions did not differ between groups, but appetite was better in dogs receiving carprofen than in dogs in the placebo group. Conclusions and Clinical Relevance—It is possible that the transient decreases in serum protein and albu- min concentrations in dogs that received carprofen were caused by altered mucosal permeability of the gastrointestinal tract because no indications of renal or hepatic toxicity were observed. Carprofen appeared to be well tolerated by dogs after 2 months of adminis- tration. (J Am Vet Med Assoc 2006;228:876–880) From the Department of Clinical Veterinary Sciences, Faculty of Veterinary Medicine, University of Helsinki, FI-00014 Helsinki, Finland. Presented in part at the Association of Veterinary Anaesthetists autumn meeting, September 2004, Vienna, Austria. Supported by the Finnish Foundation of Veterinary Research and Helvi Knuuttila Foundation. Address correspondence to Dr. Raekallio. NSAID Nonsteroidal anti-inflammatory drug ALP Alkaline phosphatase ALT Alanine aminotransferase GGT γ-Glutamyltransferase