Disease relevance of C 5720

• Carprofen reduces the structural changes and the abnormal subchondral bone metabolism of experimental osteoarthritis [1].
• The influence of liver dysfunction on the pharmacokinetics of carprofen [2].
• The efficacy of carprofen for acute gouty arthritis deserves further trial [3].
• The results of this study showed that liver dysfunction (hepatic cirrhosis) had no effect on the pharmacokinetic profile of carprofen [2].
• Occupational photoallergic contact dermatitis in a pharmaceutical worker manufacturing carprofen, a canine nonsteroidal anti-inflammatory drug [4].

Psychiatry related information on C 5720

• N-sulfonylated and N-alkylated carprofen derivatives were investigated for their inhibition and modulation of gamma-secretase, which is associated with Alzheimer's disease [5].
• Two crossover bioequivalence trials of an enantioselectively enterohepatic recycled drug, carprofen, were conducted in dogs with the same racemic oral formulation to determine: (i) the influence of feeding patterns, and (ii) the effect of the analytical method (enantioselective vs non-enantioselective) on the statistical power of the trials [6].
• Mechanical pain threshold testing at the wound showed a significant analgesic effect of carprofen [7].

High impact information on C 5720

• Serum concentration and dose-response relationships for carprofen in rheumatoid arthritis [8].
• The test drug (100 mg carprofen) was given by mouth or through a triple-lumen nasogastric tube to the upper duodenum to three normal subjects [9].
• Behavioural effects of laparotomy and analgesic effects of ketoprofen and carprofen in rats [10].
• Probenecid inhibits the renal secretion of drug glucuronides and this will lead to accumulation in plasma of those NSAIDs eliminated primarily by the formation of labile acyl glucuronides such as naproxen, ketoprofen, indomethacin, carprofen [11].
• Our results indicate that in combination carprofen and chloral hydrate, while affording safe and reliable anesthesia and analgesia for rat ON surgery, does not affect the numbers of surviving RGCs [12].

Chemical compound and disease context of C 5720

• CONCLUSIONS AND CLINICAL RELEVANCE: Ketoprofen and carprofen given prior to surgery were effective for postoperative pain relief in dogs [13].
• Clinical evaluation of a nutraceutical, carprofen and meloxicam for the treatment of dogs with osteoarthritis [14].
• 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 [15].
• Effects of carprofen and dexamethasone on canine chondrocytes in a three-dimensional culture model of osteoarthritis [16].
• OBJECTIVE: To evaluate in vivo activity of carprofen, deracoxib, and etodolac on prostanoid production in several target tissues in dogs with chronic osteoarthritis [17].

Biological context of C 5720

• Ibuprofen at a 5:1 molar ratio to HSA displaces carprofen at a molar ratio of 1:1 to HSA from its high affinity binding site (site II) to its low affinity site (site I), as shown by production of the CD spectrum similar to that obtained in the case of the carprofen-HSA complex at a molar ratio 3:1 [18].
• The rate and extent of carprofen absorption were characterized by evaluation of the maximum plasma concentrations (Cmax), the time of their occurrence (tmax), absolute bioavailabilities, statistical moments, and by deconvolution [19].
• The influence of carprofen and indomethacin on renal salt and water homeostasis was investigated [20].
• Carprofen is eliminated predominantly by biotransformation in these three species [21].
• Indomethacin and Ro 20-5720 also enhanced the antibody response to chicken serum albumin (CSA) in buffered saline [22].

Anatomical context of C 5720

• Carprofen was the most effective compound causing an up to 500-fold increase of CMA-induced IFN production in pure bone marrow-derived macrophages [23].
• Pharmacokinetics of carprofen in plasma and synovial fluid [24].
• In dogs, biliary secretion predominates, and 70% of an intravenous dose of carprofen is excreted in the feces while 8--15% of the dose is excreted in the urine [21].
• Carprofen treatment also delays and/or prevents the abnormal metabolism of subchondral osteoblasts in this model [25].
• Indomethacin and Ro 20-5720, two prostaglandin synthesis inhibitors, produced a several-fold enhancement of the primary immunoglobulin (Ig) M and IgG anti-sheep red blood cell plaque-forming cell (PFC) response in CAF1 mice [22].

Associations of C 5720 with other chemical compounds

• The stereoselective binding of carprofen enantiomers and carprofen glucuronide diastereomers to human serum albumin (HSA) was studied using an ultrafiltration method [26].
• Enhancement by carprofen or indomethacin of interferon induction by 10-carboxymethyl-9-acridanone in murine cell cultures [23].
• The influence of the hydrophilicity of fatty suppository bases on the rectal absorption of the lipophilic drug carprofen (octanol-buffer, pH 7.4; partition coefficient, 40) was investigated in dogs [19].
• A rapid sensitive determination of carprofen and zomepirac using thin-layer chromatography and gas chromatography--mass spectrometry [27].
• The S(+) enantiomeric form of carprofen was found to be COX-2 selective in cats, but meloxicam was only slightly preferential for this isoenzyme [28].

Gene context of C 5720

• OBJECTIVE: To determine whether the nonsteroidal anti-inflammatory drugs (NSAIDs) carprofen, flunixin meglumine, and phenylbutazone have cyclooxygenase (COX)-independent effects that specifically inhibit activation of the proinflammatory transcription factor nuclear factor kappa B (NfkappaB) [29].
• RESULTS: Aspirin, diclofenac, indomethacin, ketoprofen, meclofenamic acid, and piroxicam had little selectivity toward COX isozymes, whereas NS398, carprofen, tolfenamic acid, nimesulide, and etodolac had more than 5 times greater preference for inhibiting COX-2 than COX-1 [30].
• CLINICAL RELEVANCE: The selectivity of carprofen for canine COX2 may be an important factor for its use in dogs [31].
• Activity of carprofen and other NSAID against COX1 and COX2 was compared [31].
• Indomethacin suppressed plasma renin activity more than carprofen [20].

Analytical, diagnostic and therapeutic context of C 5720

• Circular dichroism data suggested different mechanisms for the high affinity and the low affinity binding of carprofen to HSA [32].
• Reference diastereomeric glucuronides of carprofen were purified from human urine after oral administration of the single enantiomers [33].
• Following every drug administration, blood samples were collected over a period of 104 h and carprofen plasma concentrations were measured by a specific HPLC method with UV detection [19].
• Analysis of carprofen dosage forms and drug substance by high-performance liquid chromatography [34].
• The calculation of the tubular transit rate at each carprofen concentration indicated the following net mechanism(s) of renal carprofen clearance: filtration at low concentration, reabsorption at intermediate concentrations, and secretion at the highest concentration [35].

References