Administration Of Carprofen Research Articles

Effect of carprofen on hemostatic variables in dogs.

To evaluate the effect of carprofen on hemostatic variables in clinically normal dogs. 12 clinically normal Labrador Retrievers. 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. 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. 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.

Plasma and synovial concentrations of carprofen in dogs with chronic osteoarthritis

SummaryThe objective of this study was to measure the synovial and plasma concentration of carprofen in normal and osteoarthritic stifle joints throughout a 12-hour period. Eight healthy male mixed breed hound dogs with chronic right stifle osteoarthritis (OA) secondary to right cruciate ligament transection, were used. Each dog was treated with carprofen (2mg/kg every 12 hours) for 14 days at four different time periods. Prior to treatment, each dog had baseline data collected that included two force plate evaluations (seven days apart), synovial fluid, and plasma collections. Plasma samples were collected at three hours post drug administration on days two, four, six, eight, 10, and 12. On days #7 and 14 plasma, serum, bilateral stifle synovial fluid and ground reaction forces (GRFs) were collected at three, six, nine, or 12 hours post-medication, depending upon the test protocol. Vertical and cranio-caudal ground reaction forces were recorded at each time period. Plasma concentrations measured at three hours remained constant over each testing protocol. There were not any differences between the plasma carprofen concentrations at three, nine, or 12 hours between days #7 or 14. A significant difference was not found in the carprofen synovial concentrations between left and right stifles at any time. Significant increases in vertical impulse data were found at six hours post-treatment, for all of the collection periods on days three, seven and 14. During the study, there was not any indication that carprofen had a ‘preference’ for the OA stifle as opposed to the normal stifle. Carprofen administration increased the total force transmitted through the abnormal limb.Carprofen concentrations in the plasma and synovial fluid and ground reaction forces were measured in dogs with single stifle osteoarthritis at three, six, nine and 12 hours following dosing at 2 mg/kg every 12 hours. Carprofen did not have a ‘preference’ for the OA stifle as opposed to the normal stifle. Carprofen administration increased the total force transmitted through the abnormal limb.

Effects of butorphanol and carprofen on the minimal alveolar concentration of isoflurane in dogs

To evaluate the effects of butorphanol and carprofen, alone and in combination, on the minimal alveolar concentration (MAC) of isoflurane in dogs. Randomized complete-block crossover study. 6 healthy adult dogs. Minimal alveolar concentration of isoflurane was determined following administration of carprofen alone, butorphanol alone, carprofen and butorphanol, and neither drug (control). Anesthesia was induced with isoflurane in oxygen, and MAC was determined by use of a tail clamp method. Three hours prior to induction of anesthesia, dogs were fed a small amount of canned food without any drugs (control) or with carprofen (2.2 mg/kg of body weight [1 mg/lb]). Following initial determination of MAC, butorphanol (0.4 mg/kg [0.18 mg/lb], i.v.) was administered, and MAC was determined again. Heart rate, respiratory rate, indirect arterial blood pressure, endtidal partial pressure of CO2, and saturation of hemoglobin with oxygen were recorded at the time MAC was determined. Mean +/- SD MAC of isoflurane following administration of butorphanol alone (1.03 +/- 0.22%) or carprofen and butorphanol (0.90 +/- 0.21%) were significantly less than the control MAC (1.28 +/- 0.14%), but MAC after administration of carprofen alone (1.20 +/- 0.13%) was not significantly different from the control value. The effects of carprofen and butorphanol on the MAC of isoflurane were additive. There were not any significant differences among treatments in regard to cardiorespiratory data. Results suggest that administration of butorphanol alone or in combination with carprofen significantly reduces the MAC of isoflurane in dogs; however, the effects of butorphanol and carprofen are additive, not synergistic.

The Gastroduodenal Effects of Buffered Aspirin, Carprofen, and Etodolac in Healthy Dogs

Twenty‐four healthy mixed‐breed dogs were divided into 4 groups. Group 1 received a placebo PO q12h, group 2 received an average of 16.5 (15.1–17.8) mg/kg buffered aspirin PO q12h, group 3 received an average of 2.2 (2.0–2.4) mg/kg carprofen PO q 12h, and group 4 received an average of 12.8 (11.7–13.8) mg/kg etodolac PO q24h (with a placebo in the PM). All treatments continued for 28 consecutive days. Gastroduodenal endoscopy was performed on days —9, 0, 5, 14, and 28. Multiple gastric biopsies were obtained endoscopically on day —9 to determine each dog's Helicobacter infection status. Four regions in the stomach and 1 region in the proximal duodenum were evaluated endoscopically, and each was assigned a score from 1 to 11. Scores for each region then were summed to give a total score for each endoscopic evaluation. Erosions and submucosal hemorrhages were seen in all dogs receiving aspirin. Only minor gastric lesions were observed in the carprofen, etodolac, and control groups. No adverse clinical signs were noted in any dog given any treatment. Median total score on days 0, 5, 14, and 28, respectively, were as follows: group 1: 5.0, 5.0, 5.0, 5.0; group 2: 5.0, 27.0, 26.0, 27.5; group 3: 5.0, 5.0, 6.0, 5.0; group 4: 5.0, 7.0, 5.0, 5.0. There was no significant difference among dogs receiving carprofen, etodolac, or placebo. The administration of carprofen, etodolac, or placebo to healthy dogs resulted in significantly less gastroduodenal lesion development than in dogs receiving buffered aspirin.

Comparison of the effects of oral or subcutaneous carprofen or ketoprofen in rats undergoing laparotomy

Rats undergoing laparotomy received either carprofen (5 mg/kg) or ketoprofen (5 mg/kg) administered orally in flavoured gelatin, or by subcutaneous injection. A control group that received no analgesic showed a...

Hepatocellular toxicosis associated with administration of carprofen in 21 dogs

Hepatocellular toxicosis associated with administration of carprofen in 21 dogs

Biopharmaceutical evaluation of carprofen following single intravenous, oral, and rectal doses in dogs

Absorption and disposition characteristics of carprofen were compared in the dog after intravenous, oral, and rectal administrations. Rectal formulations included an aqueous solution and a suppository. Single doses of 100 mg carprofen were given in a cross-over design and plasma concentrations of unchanged drug were determined by HPLC. Plasma concentration-time profiles could be adequately described after intravenous and extravascular administrations by tri-and biexponential functions, respectively. After intravenous applications the basic disposition parameters could be determined: mean (+/- S.D.) elimination half-life was about 11.7 (+/- 3.1) h; volume of distribution ranged from 0.12 to 0.22 l kg-1 and total plasma clearance was about 0.017 +/- 0.003 l h kg-1. After oral dosing, carprofen was rapidly absorbed (time of maximum concentration: 0.83 +/- 0.61 h) and comparison with the intravenous solution indicated complete bioavailability. After rectal administration, the rate of absorption evaluated through tmax and calculation of mean absorption times was always slower than after oral dosing. Relative bioavailabilities of the drug from the suppository were about 20 per cent lower than from rectal solutions. No significant difference in rates of absorption of carprofen from rectal solution and suppository was seen; this allowed the conclusion that drug release from the semi-solid dosage form was not the rate-limiting step in carprofen absorption from the suppository. From the present study, it is concluded that rectal administration of carprofen offers an alternative to the oral route of drug intake.

Determination of the anti-inflammatory agent carprofen, ( d,l)-6-chloro-α-methylcarbazole-2-actic acid, in blood by high-pressure liquid chromatography

A rapid, sensitive, and specific high-pressure liquid chromatographic (HPLC) assay was developed for the determination of ( d,l)-6-chloro-α-methylcarbazole-2-acetic acid (carprofen) in blood. The assay involves extraction into diethyl ether from blood buffered to pH 6. The overall recovery of carprofen from blood is 97.3 ± 5.3% (S.D.), and the sensitivity limit of detection is 100–200 ng/ml of blood using a UV detector at 254 nm or 3 ng/ml of blood using a fluorescence detector with excitation at 240 nm and emission at wavelengths greater than 350 nm. The HPLC assay is amenable to rapid routine analysis of clinical specimens, and the data obtained using this assay showed an excellent correlation coefficient (0.99) compared with a previously published spectrofluorometric assay. The method was used to monitor the blood level-time fall-off profiles in four subjects following single and multiple dose administration of carprofen.

非ステロイド性抗炎症薬Carprofenの薬理学的研究

The pharmacological profile of carprofen as a new non-steroidal anti-inflammatory drug has been established in various experimental inflammation models in animals. This compound possesses marked effects on prevention of adjuvant arthritis, cotton-pellet granuloma formation and hyperalgesic edema (scalding) and the extent is similar to that observed with indomethacin and piroxicam. The anti-inflammatory potency of carprofen is markedly stronger than those seen in cases of phenylbutazone, mefenamic acid, ibufenac and acetylsalicylic acid, almost equal to that of diclofenac and slightly lower than that of indomethacin in the following parameters: carrageenin-edema, granuloma-pouch, UV-erythema, and bradykinin and histamine-induced capillary permeability. As is the case with other non-steroidal anti-inflammatory drugs, carprofen has no inhibitory effect on lethal anaphylactic shock, passive cutaneous anaphylaxis and hyperuricemia. Carprofen induces ulcerogenicity and fecal occult bleeding to a extent markedly less than those seen with indomethacin and piroxicam. These investigations on anti-inflammatory drugs indicate a probable dissimilarity to the extent of anti-inflammatory effects and induction of gastrointestinal disturbances. Repeated administration of carprofen has no effect on spontaneous excretion of corticosterone and aldosterone into adrenal vein of rats.