Renal effects of carprofen administered to healthy dogs anesthetized with propofol and isoflurane

OBJECTIVE: To evaluate renal effects of carprofen in healthy dogs following general anesthesia. DESIGN: Randomized clinical trial. ANIMALS: 10 English hound dogs (6 females and 4 males). PROCEDURE: Dogs were randomly assigned to control (n = 5) or carprofen (5) groups. Anesthesia was induced with propofol (6 to 8 mg/kg [2.7 to 3.6 mg/lb] of body weight, i.v.) and maintained with isoflurane (end-tidal concentration, 2.0%). Each dog underwent two 60-minute anesthetic episodes with 1 week between episodes, and mean arterial blood pressure was maintained between 60 and 90 mm Hg during each episode. Dogs in the carprofen group received carprofen (2.2 mg/kg [1 mg/lb], p.o.) at 9:00 AM and 6:00 PM the day before and at 7:00 AM the day of the second anesthetic episode. Glomerular filtration rates (GFR) were determined during each anesthetic episode by use of renal scintigraphy. Serum creatinine and BUN concentrations and the urine gamma-glutamyltransferase-to-creatinine concentration (urine GGT:creatinine) ratio were determined daily for 2 days before and 5 days after general anesthesia. RESULTS: Significant differences were not detected in BUN and serum creatinine concentrations, urine GGT:creatinine ratio, and GFR either between or within treatment groups over time. CONCLUSIONS AND CLINICAL RELEVANCE: Carprofen did not significantly alter renal function in healthy dogs anesthetized with propofol and isoflurane. These results suggest that carprofen may be safe to use for preemptive perioperative analgesia, provided that normal cardiorespiratory function is maintained.     

Effect of carprofen, etodolac, meloxicam, or butorphanol in dogs with induced acute synovitis

OBJECTIVE: 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. ANIMALS: 12 Beagles and 6 additional Beagles that were used only in serum CRP analyses. PROCEDURE: 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. RESULTS: 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. CONCLUSIONS AND CLINICAL RELEVANCE: 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.     

Evaluation of adverse effects of long-term oral administration of carprofen, etodolac, flunixin meglumine, ketoprofen, and meloxicam in dogs

OBJECTIVE: To evaluate adverse effects of long-term oral administration of carprofen, etodolac, flunixin meglumine, ketoprofen, and meloxicam in dogs. ANIMALS: 36 adult dogs. PROCEDURES: 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. RESULTS: 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. CONCLUSIONS AND CLINICAL RELEVANCE: 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.     

Evaluation of adverse effects of long-term orally administered carprofen in dogs

OBJECTIVE: To evaluate the adverse effects of carprofen 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 initiation 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 aminotransferase (ALT) were measured. Urinary ALP-to-creatinine, gamma-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 concentrations; ALP or ALT activity; or urinary ALP-to-creatinine, 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 albumin 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 administration.     

In vivo effects of carprofen, deracoxib, and etodolac on prostanoid production in blood, gastric mucosa, and synovial fluid in dogs with chronic osteoarthritis

OBJECTIVE: To evaluate in vivo activity of carprofen, deracoxib, and etodolac on prostanoid production in several target tissues in dogs with chronic osteoarthritis. ANIMALS: 8 dogs with chronic unilateral osteoarthritis of the stifle joint. PROCEDURE: Each dog received carprofen, deracoxib, or etodolac for 10 days with a 30- to 60-day washout period between treatments. On days 0, 3, and 10, prostaglandin (PG) E2 concentrations were measured in lipopolysaccharide-stimulated blood, synovial fluid, and gastric mucosal biopsy specimens; PGE1 concentrations were measured in gastric mucosal biopsy specimens; and thromboxane B2 (TXB2) was evaluated in blood. RESULTS: Carprofen and deracoxib significantly suppressed PGE2 concentrations in blood at days 3 and 10, compared with baseline, whereas etodolac did not. None of the drugs significantly suppressed TXB2 concentrations in blood or gastric PGE1 synthesis at any time point. All 3 drugs significantly decreased gastric synthesis of PGE2 at day 3 but not day 10 of each treatment period. All 3 drugs decreased synovial fluid PGE2 concentrations in the affected and unaffected stifle joints at days 3 and 10. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicate that carprofen and deracoxib act in vivo on target tissues as COX-1-sparing drugs by sparing gastric PGE1 and PGE2 synthesis and production of TXB2 by platelets. Etodolac also appears to be COX-1 sparing but may have variable effects on COX-2 depending on the tissue. In gastric mucosa and synovial fluid, there were no significant differences in PG production between compounds at recommended concentrations.     

Comparison of the upper gastrointestinal effects of etodolac and aspirin in healthy dogs.

Fifteen healthy castrated male dogs were separated into three treatment groups that were administered etodolac, aspirin and a placebo orally, respectively. All treatments were continued for 28 days. The animals were examined endoscopically on days 0, 3, 7, 10, 14, 17, 21, 24 and 28. There were no gastrointestinal mucosal lesions in either the etodolac or the placebo group, whereas some gastric lesions developed in the aspirin group after day 17. We considered that etodolac could be used for long-term treatments in dogs with fewer side-effects on the gastric mucosa than aspirin.     

Analgesic effects in dogs of carprofen and pethidine together compared with the effects of either drug alone

Thirty bitches undergoing routine neutering were used in an assessor-blinded trial of the postoperative analgesic effects of pethidine and carprofen administered either together or singly. The level of analgesia was assessed by visual analogue scale (VAS) scores for pain and sedation and by nociceptive mechanical threshold testing. The two drugs administered together, and carprofen alone, provided good postoperative analgesia as assessed by VAS scoring. Pethidine alone did not provide postoperative analgesia of sufficient duration.     

Effect of carprofen on hemostatic variables in dogs

OBJECTIVE: To evaluate the effect of carprofen on hemostatic variables in clinically normal dogs. ANIMALS: 12 clinically normal Labrador Retrievers. PROCEDURE: 10 dogs (6 females, 4 males) received carprofen (2.2 mg/kg of body weight, PO, q 12 h) for 5 days. Two dogs (untreated control group; 1 female, 1 male) did not receive carprofen. Hemostatic variables (platelet count, activated partial thromboplastin time, prothrombin time, fibrinogen, platelet aggregation, and bleeding time) were assessed for all dogs prior to treatment, on day 5 of treatment, and 2 and 7 days after discontinuation of the drug (days 7 and 12). Serum biochemical variables and Hct were assessed prior to treatment and on days 5 and 12. RESULTS: In dogs receiving carprofen, platelet aggregation was significantly decreased, and onset of aggregation was significantly delayed on days 5, 7, and 12, compared with pretreatment values. Activated partial thromboplastin time was significantly increased on days 5, 7, and 12 over pretreatment values in treated dogs, but values remained within reference ranges. Significant differences were not detected in buccal mucosal bleeding time, other serum biochemical and hemostatic variables, or Hct, compared with pretreatment values and the internal control group. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of carprofen for 5 days causes minor but not clinically important alterations in hemostatic and serum biochemical variables in clinically normal Labrador Retrievers. Carprofen is commonly used to treat osteoarthritis and chronic pain in dogs, but prior to this study, its effect on platelet aggregation and hemostatic variables was unknown.     

Comparison of the analgesic effects of meloxicam and carprofen administered preoperatively to dogs undergoing orthopaedic surgery

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.     

Effects of carprofen, meloxicam and deracoxib on platelet function in dogs

ObjectiveTo 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.Study designRandomized, blocked, crossover design with a 14-day washout period.AnimalsHealthy intact female Walker Hounds aged 1–6 years and weighing 20.5–24.2 kg.MethodsDogs 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 B₂ was also measured before and during administration of each drug.ResultsAll 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.Conclusions and clinical relevanceOral 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.     

Comparison of carprofen and meloxicam for 72 hours following ovariohysterectomy in dogs

OBJECTIVE: To compare the peri- and post-operative (72 hours) analgesic effects of injectable and orally administered carprofen and meloxicam for ovariohysterectomy in dogs. STUDY DESIGN: Prospective, randomized clinical study. ANIMALS: Forty-three dogs undergoing elective ovariohysterectomy. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS AND CLINICAL RELEVANCE: Both carprofen and meloxicam provided satisfactory analgesia for 72 hours following ovariohysterectomy in dogs.     

Analgesic effect of pre-operative etodolac and butorphanol administration in dogs undergoing ovariohysterectomy

The analgesic, bleeding, and renal effects of dogs pre‐medicated with etodolac with and without butorphanol were evaluated. Twenty‐four 1‐year‐old healthy dogs, weighing 19 ± 3 kg (mean ± SD) were randomly assigned to four treatment groups (n = 6): control (C), etodolac (E), butorphanol (B), and etodolac with butorphanol (EB). Etodolac (12–14 mg kg^?1 PO) was given 1 hour before propofol induction and isoflurane maintenance anesthesia. Butorphanol (0.4 mg kg^?1 IV) was given immediately following endotracheal intubation. Control dogs received only propofol (8 mg kg^?1 to effect) and isoflurane anesthesia. All dogs were mechanically ventilated to maintain Pe ′CO₂ between 35 and 45 mm Hg (4.7–6.0 kPa). Lactated Ringer's solution was given at 10 mL kg^?1 hour^?1 during anesthesia. Plasma cortisol concentrations were assessed 1 day prior to surgery (baseline), immediately prior to anesthesia induction, and every 30 minutes until 5 hours following extubation, and 1 day after surgery. Total duration of anesthesia was 50 minutes and total surgery duration was 30 minutes. Isoflurane concentration area under the curve (AUC) over time during the anesthesia was compared among treatment groups. Buccal mucosal bleeding time (BMBT) was assessed 1 day before E administration and during surgery. Urine GGT to urine creatinine ratio, BUN, and plasma creatinine were taken daily from 1 day before to 3 days after surgery. Behavioral pain scores (numerical rating scale) were assessed by two observers blinded to the treatment during the 5‐hour recovery period at 30 minute intervals until 3 hours, and again at 5 hours after extubation. All data were analyzed using anova . Multiple comparisons were performed if the anova was significant. Alpha value was set at 0.05. Plasma cortisol concentrations significantly increased from time of extubation in all the treatment groups. They did not return to the baseline until 5, 2.5, 1.5, and 1.5 hours after extubation in the C, B, E, and EB groups, respectively. Isoflurane AUC was not significantly different among treatment groups. Dogs treated with EB had significantly less behavioral pain than all other groups throughout the 5‐hour recovery period. No significant difference was found between treatment groups or within treatment groups over time in BMBT, or any renal variables. This study demonstrated that (i) pre‐operative administration of E provides profound analgesia during the post‐operative period without renal or bleeding side‐effects in dogs undergoing OHE; and (ii) a combination of butorphanol–etodolac provides the best analgesic effect during the post‐operative period based on the behavioral pain score.     

Effects of carprofen on renal function during medetomidine-propofol-isoflurane anesthesia in dogs

OBJECTIVE: To investigate effects of carprofen on indices of renal function and results of serum bio-chemical analyses and effects on cardiovascular variables during medetomidine-propofol-isoflurane anesthesia in dogs. ANIMALS: 8 healthy male Beagles. PROCEDURES: A randomized crossover study was conducted with treatments including saline (0.9% NaCl) solution (0.08 mL/kg) and carprofen (4 mg/kg) administered IV. Saline solution or carprofen was administered 30 minutes before induction of anesthesia and immediately before administration of medetomidine (20 microg/kg, IM). Anesthesia was induced with propofol and maintained with inspired isoflurane in oxygen. Blood gas concentrations and ventilation were measured. Cardiovascular variables were continuously monitored via pulse contour cardiac output (CO) measurement. Renal function was assessed via glomerular filtration rate (GFR), renal blood flow (RBF), scintigraphy, serum biochemical analyses, urinalysis, and continuous CO measurements. Hematologic analysis was performed. RESULTS: Values did not differ significantly between the carprofen and saline solution groups. For both treatments, sedation and anesthesia caused changes in results of serum biochemical and hematologic analyses; a transient, significant increase in urine alkaline phosphatase activity; and blood flow diversion to the kidneys. The GFR increased significantly in both groups despite decreased CO, mean arterial pressure, and absolute RBF variables during anesthesia. CONCLUSIONS AND CLINICAL RELEVANCE: Carprofen administered IV before anesthesia did not cause detectable, significant adverse effects on renal function during medetomidine-propofol-isoflurane anesthesia in healthy Beagles.     

Long-term treatment with carprofen of 805 dogs with osteoarthritis

The pain-relieving effect of carprofen and tolerance to the drug were investigated in 805 dogs that were lame as a result of osteoarthritis. The dogs were of different breeds, ages and bodyweights and of both sexes, and were selected from 51 veterinary clinics. Each dog was treated orally by its owner with 4 mg/kg carprofen for 84 consecutive days. Twenty-four dogs were removed from the study because of side effects, and 55 left the study for reasons unrelated to the treatment. The condition of the dogs and the benefit of the treatment were evaluated by the veterinary surgeons and the owners after 14 days, and at the end of the period of treatment, when 194 of the dogs (26.7 per cent) were no longer lame, and 357 (49.2 per cent) had improved. The period for which the dogs had been lame before entering the study significantly (P<0.01) affected the results and the rate of improvement. Too much exercise during the 84 days of treatment caused some dogs to relapse.     

Efficacy and safety of preoperative etodolac and butorphanol administration in dogs undergoing ovariohysterectomy

Eighteen dogs undergoing ovariohysterectomy were premedicated with etodolac, butorphanol, or their combination. Various parameters, such as blood pressure, isoflurane requirements, behavioral pain scores, plasma cortisol concentration, plasma glucose concentration, and mucosal bleeding time, were assessed. The integrated plasma cortisol values were significantly lower in the etodolac and etodolac with butorphanol groups. Dogs receiving etodolac and butorphanol had the lowest behavioral pain scores from extubation until the end of monitoring. Isoflurane concentration over time (area under the curve), buccal mucosal bleeding time, and indices of renal function were not significantly different among the treatment groups.     

Effect of oral administration of carprofen on intraocular pressure in normal dogs

The aim of this study was to determine the effect of oral administration of carprofen on intraocular pressure in normal dogs. Twelve young adult beagle dogs were randomly assigned to treatment (n = 6) or control (n = 6) groups. After an 11‐day acclimation period, the treatment group received approximately 2.2 mg/kg carprofen per os every 12 h for 7 days, and the control group received a placebo gel capsule containing no drug per os every 12 h for 7 days. Intraocular pressure (IOP) was measured by a rebound tonometer at three time points per day (8 am, 2 pm, and 8 pm) during the acclimation (days 1–11) and treatment (days 12–18) phases and for 48 h (days 19–20) after the completion of treatment. There was no statistically significant change in IOP for either eye in the dogs receiving oral carprofen during the treatment phase (days 12–18). After day 4, no significant daily IOP changes were seen in control group dogs. Carprofen administered orally every 12 h for 7 days had no effect on IOP in normal beagle dogs. An acclimation period to frequent IOP measurements of at least 5 days is necessary to establish baseline IOP values and minimize possible anxiety‐related effects on IOP measurements.     

The steady-state pharmacokinetics and bioequivalence of carprofen administered orally and subcutaneously in dogs

Eighteen male Beagle dogs were randomized to oral (p.o.) or subcutaneous (s.c.) carprofen administration in a two-sequence, two-period crossover design with a 10-day washout between periods. Twenty-five milligrams of carprofen was administered p.o. or s.c. every 12 h for 7 days. Plasma concentrations of carprofen collected after the first and last treatments were determined by high-performance liquid chromatography. Carprofen concentration data were natural log transformed and geometric means were calculated for maximum plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC0--12) following the first dose and Cmax and AUC0--12 following administration of the last dose. Formulations were considered bioequivalent if the 90% confidence interval (CI) of the mean difference for each variable between formulations were within -20% and 25% of the oral formulation. The mean Cmax and AUC0--12 were 16.9 microg/mL and 73.1 microg. h/mL, respectively, following a single oral dose and 8.0 microg/mL and 64.3 microg x h/mL, respectively, following a single s.c. injection. The 90% CI for Cmax (-56.8 to -48.7%) was outside of the bioequivalence criteria whereas the 90% CI for AUC0--12 (-16.3 to -7.5%) was within the bioequivalence criteria. At steady-state, the mean Cmax and AUC0--12 were 18.7 microg/mL and 101.9 microg x h/mL, respectively, following p.o. administration and 14.7 microg/mL and 111.0 microg x h/mL, respectively, following s.c. injection. The 90% CI was outside the bioequivalence criteria for Cmax (-30.8 to -10.8) but within the bioequivalence criteria for AUC0--12 (2.3-15.9%). The results of this study indicate that peak plasma concentrations of carprofen differ when administered p.o. and s.c., but that total drug exposure following a single dose and at steady-state are bioequivalent.