Pharmacokinetics of carprofen in anaesthetized pigs: a preliminary study

ObjectiveTo investigate the pharmacokinetics of carprofen after a single intravenous (IV) dose and multiple oral doses administered to pigs undergoing electroporation of the pancreas.Study designProspective experimental study.AnimalsA group of eight female pigs weighing 31.74 ± 2.24 kg (mean ± standard deviation).MethodsCarprofen 4 mg kg^?1 was administered IV after placement of a central venous catheter during general anaesthesia with isoflurane. Blood samples were collected 30 seconds before and 5, 10, 20, 30 and 60 minutes and 2, 4, 6, 8, 12 and 24 hours after carprofen administration. Subsequently, the same dose of carprofen was administered orally, daily, for 6 consecutive days and blood collected at 36, 48, 60, 72, 96, 120, 144 and 168 hours after initial carprofen administration. Plasma was analysed using liquid chromatography with mass spectrometry. Standard pharmacokinetic parameters were calculated by compartmental analysis of plasma concentration–time curves. Data are presented as mean ± standard error.ResultsThe initial plasma concentration of IV carprofen was estimated at 54.57 ± 3.92 μg mL^?1 and decreased to 8.26 ± 1.07 μg mL^?1 24 hours later. The plasma elimination curve showed a bi-exponential decline: a rapid distribution phase with a distribution half-life of 0.21 ± 0.03 hours and a slower elimination phase with an elimination half-life of 17.31 ± 3.78 hours. The calculated pharmacokinetic parameters were as follows: the area under the plasma concentration–time curve was 357.3 ± 16.73 μg mL^?1 hour, volume of distribution was 0.28 ± 0.07 L kg^?1 and plasma clearance rate was 0.19 ± 0.009 mL minute^?1 kg^?1. The plasma concentration of carprofen, administered orally from days 2 to 7, varied from 9.03 ± 1.87 to 11.49 ± 2.15 μg mL^?1.Conclusions and clinical relevanceCarprofen can be regarded as a long-acting non-steroidal anti-inflammatory drug in pigs.     

Pharmacokinetics and bioavailability of oral firocoxib in adult,mixed‐breed goats

Pharmacokinetic (PK) studies of oral firocoxib in large animal species have been limited to horses, preruminating calves, and adult camels. The aim of this study was to describe pharmacokinetics and bioavailability of firocoxib in adult goats. Ten healthy adult goats were administered 0.5 mg/kg firocoxib intravenously (i.v.) and per os (p.o.) in a randomized, crossover study. Plasma firocoxib concentrations were measured over a 96‐hr period for each treatment using HPLC and mass spectrometry, and PK analysis was performed. The p.o. formulation reached mean peak plasma concentration of 139 ng/ml (range: 87–196 ng/ml) in 0.77 hr (0.25–2.00 hr), and half‐life was 21.51 hr (10.21–48.32 hr). Mean bioavailability was 71% (51%–82%), indicative of adequate gastrointestinal absorption of firocoxib. There were no negative effects observed in any animal, and all blood work values remained within or very near reference range at the study's conclusion. Results indicate that oral firocoxib is well‐absorbed and rapidly reaches peak plasma concentrations, although the concentration also decreased quickly prior to the terminal phase. The prolonged half‐life may suggest tissue accumulation and higher plasma concentrations over time, depending on dosing schedule. Further studies to determine tissue residue depletion, pharmacodynamics, and therapeutic concentrations of firocoxib in goats are necessary.     

Pharmacokinetics and tissue concentrations of firocoxib in sows following oral administration

The objectives of this study were to describe the pharmacokinetics of firocoxib following oral (PO) dosing and intravenous (IV) injection in sows. Seven healthy sows were administered 0.5 mg firocoxib/kg IV. Following a 23-d washout period, sows were administered firocoxib at 4.0 mg firocoxib/kg PO. Blood samples were collected at predetermined times for 72 hr after IV and 120 hr after PO administration. Plasma firocoxib concentration was measured using UPLC-MS/MS, and pharmacokinetic analysis was performed using noncompartmental procedures. Tissue firocoxib concentrations were determined at 5, 10 (n = 2/time point), and 21 d (n = 3) after PO administration. The geometric mean half-life following IV and PO administration was 16.6 and 22.5 hr, respectively. A mean peak plasma concentration (Cmax) of 0.06 µg/ml was recorded at 7.41 hr (T_max) after oral administration. Mean oral bioavailability was determined to be 70.3%. No signs of NSAID toxicity were observed on macroscopic and microscopic investigation. Firocoxib was detected in the skin with subcutaneous fat (0.02 µg/g) of one of three sows at 21 days postadministration. Additional work to establish appropriate meat withhold intervals in sows is required. Firocoxib was readily absorbed following PO administration. Further work is needed to better understand the analgesic effects for sows and piglets nursing sows administered firocoxib.     

Comparison between analgesic effects of buprenorphine, carprofen, and buprenorphine with carprofen for canine ovariohysterectomy

OBJECTIVE: To compare the analgesic effects of buprenorphine, carprofen, and their combination in dogs undergoing ovariohysterectomy. STUDY DESIGN: Prospective, randomized blinded clinical study. ANIMALS: 60 dogs. METHODS: Treatments were buprenorphine 0.02 mg kg(-1), intramuscularly (IM) (group B); carprofen 4 mg kg(-1), subcutaneously (SC) (group C); or a combination of both (group CB). Anesthesia was induced with propofol and maintained with isoflurane. A Dynamic Interactive Visual Analog Scale (DIVAS, 0-100 mm) and the Glasgow Composite Pain Scale (GCMPS, 0-24) were used to evaluate comfort and sedation at baseline, 2, 4, 6, and 24 hours after extubation. Rescue analgesia was provided with buprenorphine (0.02 mg kg(-1)). Wound swelling measurements (WM) and a visual inflammation score (VIS) of the incision were made after surgery and 2, 4, 6, and 24 hours later. p < 0.05 was considered significant. RESULTS: Group C required more propofol (5.0 +/- 1.4 mg kg(-1)) compared with B (3.3 +/- 1.1 mg kg(-1)) and CB (3.2 +/- 0.7 mg kg(-1)); respectively, p = 0.0002 and 0.0001. Rescue analgesia was required in nine dogs. B had a higher GCMPS and DIVAS III score at 6 hours (2.6 +/- 2.5) and (23 +/- 22.5 mm) compared with C (1.0 +/- 1.3, 6 +/- 7.3 mm) and CB (1.5 +/- 1.4, 8 +/- 10.7 mm); respectively, p = 0.02 and 0.006. Group C had a lower sedation score at 2 hours (43 +/- 23.6 mm) compared with B (68 +/- 32.1 mm) and BC (69 +/- 22.1 mm); respectively, p = 0.03 and 0.004. Group B had a higher WM score at 2 hours (3 +/- 0.8 mm) compared with C (2 +/- 0.6 mm) p = 0.01 and at 6 hours (3 +/- 1 mm) compared with C (2 +/- 0.8 mm) and CB (2 +/- 0.8 mm); respectively, p = 0.01 and 0.008. VIS was not different between groups. CONCLUSION AND CLINICAL RELEVANCE: All treatments provided satisfactory analgesia for the first 6 hours and at 24 hours. C and CB pain score and WS were superior to B at 6 hours. No superior analgesic effect was noted when the drugs were combined.     

A study of the pharmacokinetics and thromboxane inhibitory activity of a single intramuscular dose of carprofen as a means to establish its potential use as an analgesic drug in white rhinoceros

The alleviation of pain and prevention of suffering are key aspects of animal welfare. Unfortunately, analgesic drugs are not available for all species. White rhinoceros (Ceratotherium simum ), representing one of such species, which survive poaching attempts inflicted with severe facial injuries and gunshot wounds, nonetheless require analgesic support. To improve treatment conditions, this study explored the use of carprofen for the treatment of pain and inflammation in white rhinoceros. The pharmacokinetics of 1 mg/kg intramuscular carprofen was evaluated in six healthy white rhinoceros. The half‐life of λ_z and mean residence time was 105.71 ± 15.67 and 155.01 ± 22.46 hr, respectively. The area under the curve and the maximum carprofen concentration were 904.61 ± 110.78 μg ml^?1 hr^?1 and 5.77 ± 0.63 μg/ml, respectively. Plasma TXB ₂ inhibition demonstrated anti‐inflammatory properties and indicated that carprofen may be effective for a minimum of 48 hr in most animals. With its long half‐life further indicating that a single dose could be effective for several days, we suggest that carprofen may be a useful drug for the treatment of white rhinoceros.     

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.     

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.     

Rickets in a litter of racing greyhounds

Rickets was diagnosed in six 14-week-old racing greyhound littermates presented with musculoskeletal disease. Physical findings included listlessness, profound muscle weakness, lameness, lateral bowing of the antebrachll and focal hard swellings proximal to the tarsi and carpl. Radiological findings included generallsed osteopenia, axial and radial thickening of growth plates, and 'cupping' of the adjacent metaphyses; the distal ulnar growth plates were most severely and consistently affected. The diagnosis was confirmed by demonstrating subnormal concentrations of 2bhydroxycholecalciferol in serum samples collected at admission. The pups' diet consisted of an inexpensive generic kibble formulated for adult dogs, porridge, milk, pasta, minced beef, vegetables and a small quantity of calcium carbonate powder. The pups were successfully treated by feeding a nutritionally complete, vitamin D-containing ration formulated for growing pups. Bilateral growth retardation of distal ulnar physes occurred as a sequel In one pup.     

Comparison of preoperative carprofen and postoperative butorphanol as postsurgical analgesics in cats undergoing ovariohysterectomy

OBJECTIVE: To compare carprofen to butorphanol, with regard to postsurgical analgesic effects, duration of analgesia, and adverse side effects. STUDY DESIGN: Blinded, randomized clinical study. ANIMALS: Seventy-one cats, 0.5-5 years of age, weighing 3.24 +/- 0.61 kg, undergoing ovariohysterectomy (OHE). METHODS: Cats were premedicated with subcutaneous atropine (0.04 mg kg(-1)), acepromazine (0.02 mg kg(-1)), and ketamine (5 mg kg(-1)). Anesthesia was induced with ketamine (5 mg kg(-1)) and diazepam (0.25 mg kg(-1)) given intravenously, and maintained with isoflurane. There were three treatment groups: group C (4 mg kg(-1) carprofen SC at induction), group B (0.4 mg kg(-1) butorphanol SC at end of surgery), and group S (0.08 mL kg(-1) of sterile saline SC at induction and end of surgery). Behavioral data were collected using a composite pain scale (CPS), prior to surgery (baseline) and 1, 2, 3, 4, 8, 12, 16, 20, and 24 hours post-surgery. Interaction scores were analyzed separately. Cats with CPS scores >12 received rescue analgesia (meperidine, 4 mg kg(-1), intramuscular). RESULTS: Sixty cats completed the study. The CPS scores did not differ significantly between groups C and B at any time period. CPS scores for groups B and C were significantly increased for 12 hours post-surgery, and in group S for 20 hours. Both group C and B CPS scores were significantly lower than group S in this 20-hour postoperative period, except at 4 hours (B and C) and at 3 and 8 hours (B alone). Interaction scores for group C returned to preoperative baseline 4 hours after surgery, while both groups B and S remained increased for at least 24 hours post-surgery. Nine cats required meperidine. CONCLUSION: In this study, carprofen provided better postsurgical analgesia than butorphanol. Clinical relevance Neither drug completely abolished pain, however preoperative carprofen provided better pain control compared with postoperative butorphanol in the 24-hour period following OHE surgery in cats.     

Effects of buprenorphine, carprofen and saline on thermal and mechanical nociceptive thresholds in cats

OBJECTIVE: To evaluate a prototype pressure stimulus device for use in the cat and to compare with a known thermal threshold device. ANIMALS: Eight healthy adult cats weighing between 3.0 and 4.9 kg. METHODS: Pressure stimulation was given via a plastic bracelet taped around the forearm. Three 2.4 mm diameter ball bearings, in a 10-mm triangle, were advanced against the craniolateral surface of the antebrachium by manual inflation of a modified blood pressure bladder. Pressure in the cuff was recorded at the end point (leg shake and head turn). Thermal threshold was also tested. Stimuli were stopped if they reached 55 degrees C or 450 mmHg without response. After four pressure and thermal threshold baselines, each cat received SC buprenorphine 0.01 mg kg(-1), carprofen 4 mg kg(-1) or saline 0.3 mL in a three period cross-over study with a 1-week interval. The investigator was blinded to the treatment. Measurements were made at 0.25. 0.5, 0.75, 1, 2, 3, 4, 6, 8, and 24 hours after injection. Data were analyzed by using ANOVA. RESULTS: There were no significant changes in thermal or pressure threshold after administration of saline or carprofen, but thermal threshold increased from 60 minutes until 8 hours after administration of buprenorphine (p < 0.05). The maximum increase in threshold from baseline (DeltaT(max)) was 3.5 +/- 3.1 degrees C at 2 hours. Pressure threshold increased 2 hours after administration of buprenorphine (p < 0.05) when the increase in threshold above baseline (DeltaP(max)) was 162 +/- 189 mmHg. CONCLUSIONS AND CLINICAL RELEVANCE: This pressure device resulted in thresholds that were affected by analgesic treatment in a similar manner but to a lesser degree than the thermal method. Pressure stimulation may be a useful additional method for analgesic studies in cats.     

Clinical evaluation of firocoxib and carprofen for the treatment of dogs with osteoarthritis

A double-blind, randomised, controlled, multicentre field study was conducted to compare the safety and efficacy of firocoxib chewable tablets and carprofen tablets in 218 dogs with osteoarthritis. Firocoxib is a non-steroidal anti-inflammatory drug with more than 350-fold selectivity in dogs for the inducible isoform of the enzyme cyclo-oxygenase-2. The efficacy, tolerance and ease of administration of firocoxib (5 mg/kg/day) and carprofen (4 mg/kg/day) were assessed by the owners and the attending veterinarians during 30 days of treatment. The efficacy was assessed in terms of the dogs' overall scores at the end of the treatment, based on the veterinarians' assessment of lameness, pain on manipulation/palpation, range of motion, and joint swelling; 92.5 per cent of the dogs treated with firocoxib and 92.4 per cent of the dogs treated with carprofen had improved. The reduction in lameness in the dogs treated with firocoxib was significantly greater than in the dogs treated with carprofen. The owners' evaluations were that 96.2 per cent of the dogs treated with firocoxib and 92.4 per cent of the dogs treated with carprofen had improved, and this difference was statistically significant.     

Genetic analysis of racing performance in Irish greyhounds

The aim of this study was to analyse racing performance data in Irish greyhounds with regard to genetic and environmental variation. Estimation of heritabilities for racing time (RT) and ranking, and the prediction of breeding values for all greyhounds in the investigated data were carried out. Data from 42,785 races in Ireland in the years 2000-2003 were available. These results were obtained from 42,880 greyhounds on 20 race tracks over a distance of 480 m. Three traits were analysed, RT, ranking and a scaled logarithmic function for RT (ART), which was used to adjust racing time to be normally distributed. The data were analysed with a bivariate animal model. The estimated heritabilities were moderate for RT (0.31) and ART (0.38), but very low for ranking (0.10). The repeatabilities were 0.56 (RT), 0.51 (ART) and 0.13 (ranking). The genetic correlations were very high, 0.99 (RT-ranking) and 0.96 (ART-ranking), while the phenotypic correlation was lower, 0.60 (RT-ranking) and 0.62 (ART-ranking). The genetic trend for the traits as well as the phenotypic change of the average RT was positive.     

Pharmacokinetics and Pharmacodynamics of Dexamethasone after Intravenous Administration in Camels: Effect of Dose

The pharmacokinetics and pharmacodynamics of dexamethasone were evaluated in healthy camels after single intravenous bolus doses of 0.05, 0.1 and 0.2 mg/kg body weight. Dexamethasone showed dose-independent pharmacokinetics. The pharmacokinetic parameters of the two-compartment pharmacokinetic model for the lowest intravenous dose (mean+/-SD) were as follows: terminal elimination half-life 8.17 +/- 1.79 h; total body clearance 100.7 +/- 52.1 (ml/h)/kg; volume of distribution at steady state 0.95 +/- 0.23 L/kg; and volume of the central compartment 0.22 +/- 0.07 L/kg. The extent of plasma protein binding was linear over the concentration range 5-100 ng/ml and averaged 75% +/- 2%. Pharmacodynamic effects were evaluated by measuring endogenous plasma cortisol concentrations, numbers of circulating lymphocytes and neutrophils and plasma glucose concentrations and were analysed using indirect pharmacokinetic/pharmacodynamic models. The cumulative systemic effect increased with dose for markers of pharmacodynamic activity. The estimated IC50 of dexamethasone for cortisol and lymphocytes for the lowest dose were 3.74 +/- 2.44 and 5.58 +/- 8.37 ng/ml, respectively and the EC50 values for neutrophils and glucose were 45.8 +/- 36.9 and 1.17 +/- 0.71 ng/ml, respectively.     

Thromboelastographic tracings in retired racing greyhounds and in non-greyhound dogs

BACKGROUND: Bleeding disorders in patients with normal coagulation test results are frequently reported in Greyhounds. The purpose of this study was to compare Greyhounds to non-Greyhounds by thromboelastography (TEG). HYPOTHESIS: TEG parameters in Greyhounds are different from those in non-Greyhounds. ANIMALS: Forty-three healthy dogs (28 Greyhounds and 15 non-Greyhounds) based on the results of physical examination, CBC, activated partial thromboplastin time, prothrombin time, fibrinogen, and platelet count. MATERIALS AND METHODS: Recalcified citrated native TEGs were performed in both groups; data were compared using Student's, Mann-Whitney, and Pearson's statistical tests. RESULTS: In Greyhounds, mean +/- SD were as follows: R-time 4.3 +/- 1.7 minutes, K-time 3.8 +/- 1.4 minutes, angle (alpha) 50.0 +/- 8.0 degrees , maximum amplitude (MA) 47.6 +/- 5.6 mm, clot strength (G) 4,647 +/- 1,097 dyn/cm2, and percent lysis at 60 minutes (LY60) 2.8 +/- 5.0%. In the non-Greyhounds they were R-time 3.7 +/- 1.6 minutes, K-time 2.5 +/- 0.9 minutes, angle 59.8 +/- 7.0 degrees , MA 53.1 +/- 5.6 mm, G 5,811 +/- 1,256 dyn/cm2, and LY60 3.1 +/- 2.5%. All parameters were significantly different between the groups, except for R-time and LY60. CONCLUSION: In Greyhounds, clotting kinetics are slower and clot strength are weaker than in non-Greyhounds, supporting the increased tendency to bleed observed after minor trauma or surgical procedures in the breed. The findings may also be attributed to blood viscosity or to the concentration of citrate in the sample (ie, Greyhounds have higher hematocrit and less plasma per unit volume).     

Age at first start and racing career of a cohort of Australian Standardbred horses

OBJECTIVE Compare the career profiles of a cohort of Standardbred horses that first raced as 2-year-olds with those that started their racing careers at a later age. METHOD Retrospective analysis of the racing records of all foals born in New South Wales in the 2000 foaling season. RESULTS The career records of 999 horses were analysed. Almost half (43.9%) first raced as 2-year-olds and one-third (33.9%) as 3-year-olds. The median career duration for horses that first raced as 2-year-olds was 2.93 years (interquartile range (IQR) 2.70-3.16), which was significantly greater than the median for horses that first raced at 3, 4 or ≥5 years old (P < 0.001). Males, and horses that first raced as 2-year-olds, earned significantly more prize money than females or horses that started racing aged ≥3 years (P < 0.001). The population median number of career starts was 28.0 (IQR 8-64). Males, and horses that first raced as 2-year-olds, had significantly more career starts than females or horses that started racing aged ≥3 years (P < 0.001). CONCLUSION This study found no evidence suggesting that racing as a 2-year-old had a deleterious effect on a horse's racing career.     

Effects of racing on hematologic and serum biochemical values in greyhounds

Blood samples were collected on nonracing days from 57 racing Greyhounds at 2 weeks, 8 weeks, 13 weeks, and 16 weeks after the beginning of the racing season. Hematologic and biochemical tests were performed to detect marked changes induced by stress of racing. In general, these Greyhounds were healthy. Rhabdomyolysis was detected in one dog. In several other dogs, possible subclinical muscle injury was identified by increased serum creatine kinase activities. Mean serum Ca concentrations tended to decrease during the racing season. None of the tests was a good predictor of racing performance. Mean values for several hematologic and biochemical tests were different from those of other breeds of dogs.