Carprofen

Carprofen inhibits canine COX2 with IC50 of 0.03 mM.

Interaction between maropitant and carprofen on sparing of the minimum alveolar concentration for blunting adrenergic response (MAC-BAR) of sevoflurane in dogs.[Pubmed:28111373]

J Vet Med Sci. 2017 Mar 18;79(3):502-508.

Maropitant, a neurokinin-1 receptor antagonist, may provide analgesic effects by blocking pharmacological action of substance P. Carprofen is a non-steroidal anti-inflammatory drug commonly used for pain control in dogs. The purpose of this study was to evaluate the effect of a combination of maropitant and Carprofen on the minimum alveolar concentration for blunting adrenergic response (MAC-BAR) of sevoflurane in dogs. Six healthy adult beagle dogs were anesthetized with sevoflurane four times with a minimum of 7-day washout period. On each occasion, maropitant (1 mg/kg) alone, Carprofen (4 mg/kg) alone, a combination of maropitant (1 mg/kg) and Carprofen (4 mg/kg), or saline (0.1 ml/kg) was subcutaneously administered at 1 hr prior to the first electrical stimulation for the sevoflurane MAC-BAR determination. The sevoflurane MAC-BAR was significantly reduced by maropitant alone (2.88 +/- 0.73%, P=0.010), Carprofen alone (2.96 +/- 0.38%, P=0.016) and the combination (2.81 +/- 0.51%, P=0.0003), compared with saline (3.37 +/- 0.56%). There was no significant difference in the percentage of MAC-BAR reductions between maropitant alone, Carprofen alone and the combination. The administration of maropitant alone and Carprofen alone produced clinically significant sparing effects on the sevoflurane MAC-BAR in dogs. However, the combination of maropitant and Carprofen did not produce any additive effect on the sevoflurane MAC-BAR reduction. Anesthetic premedication with a combination of maropitant and Carprofen may not provide any further sparing effect on anesthetic requirement in dogs.

Antimicrobial synergy between carprofen and doxycycline against methicillin-resistant Staphylococcus pseudintermedius ST71.[Pubmed:27342694]

BMC Vet Res. 2016 Jun 24;12(1):126.

BACKGROUND: New therapeutic strategies are needed to face the rapid spread of multidrug-resistant staphylococci in veterinary medicine. The objective of this study was to identify synergies between antimicrobial and non-antimicrobial drugs commonly used in companion animals as a possible strategy to restore antimicrobial susceptibility in methicillin-resistant Staphylococcus pseudintermedius (MRSP). RESULTS: A total of 216 antimicrobial/non-antimicrobial drug combinations were screened by disk diffusion using a clinical MRSP sequence type (ST) 71 strain resistant to all six antimicrobials tested (ampicillin, ciprofloxacin, clindamycin, doxycycline, oxacillin and trimethoprim/sulfamethoxazole). The most promising drug combination (doxycycline-Carprofen) was further assessed by checkerboard testing extended to four additional MRSP strains belonging to ST71 or ST68, and by growth inhibition experiments. Seven non-antimicrobial drugs (bromhexine, acepromazine, amitriptyline, clomipramine, Carprofen, fluoxetine and ketoconazole) displayed minimum inhibitory concentrations (MICs) ranging between 32 and >4096 mg/L, and enhanced antimicrobial activity of one or more antimicrobials. Secondary screening by checkerboard assay revealed a synergistic antimicrobial effect between Carprofen and doxycycline, with the sum of the fractional inhibitory concentration indexes (SigmaFICI) ranging between 0.3 and 0.5 depending on drug concentration. Checkerboard testing of multiple MRSP strains revealed a clear association between synergy and carriage of tetK, which is a typical feature of MRSP ST71. An increased growth inhibition was observed when MRSP ST71 cells in exponential phase were exposed to 0.5/32 mg/L of doxycycline/Carprofen compared to individual drug exposure. CONCLUSIONS: Carprofen restores in vitro susceptibility to doxycycline in S. pseudintermedius strains carrying tetK such as MRSP ST71. Further research is warranted to elucidate the molecular mechanism behind the identified synergy and its linkage to tetK.

Carprofen neither reduces postoperative facial expression scores in rabbits treated with buprenorphine nor alters long term bone formation after maxillary sinus grafting.[Pubmed:27473985]

Res Vet Sci. 2016 Aug;107:123-131.

In connection with bilateral maxillary sinus augmentation, the acute effects of the nonsteroidal anti-inflammatory drug Carprofen on facial expressions and long-term effects on bone formation were evaluated in 18 male New Zealand White rabbits. A 10x10mm bone window was drilled in the maxilla, the sinus membrane elevated and a titanium mini-implant inserted. One of two test materials was randomly inserted unilaterally and bovine bone chips (control) on the contralateral side in the created space. Rabbits were randomly allocated to receive buprenorphine plus Carprofen (n=9) or buprenorphine plus saline (n=9) postoperatively. Buprenorphine was administered subcutaneously every 6h for 3days in a tapered dose (0.05-0.01mg/kg) and Carprofen (5mg/kg) or saline administered subcutaneously 1h before, and daily for 4days postoperatively. To assess pain, clinical examination, body weight recording and scoring of facial expressions from photos taken before, and 6-13h after surgery were performed. Twelve weeks after surgery the rabbits were euthanized and sections of maxillary bones and sinuses were analysed with histomorphometry and by qualitative histology. Carprofen had no effect on mean facial expression scores, which increased from 0.0 to 3.6 (Carprofen) and 4.3 (saline), of a maximum of 8.0. Neither did Carprofen have an effect on bone formation or implant incorporation, whereas the test materials had. In conclusion, treatment with 5mg/kg Carprofen once daily for 5days did not reduce facial expression scores after maxillary sinus augmentation in buprenorphine treated rabbits and did not affect long term bone formation.

Effects of preoperative carprofen on cardio-respiratory, hormonal and metabolic stress response in calves during umbilical surgery under isoflurane inhalation anaesthesia.[Pubmed:27687921]

Vet J. 2016 Oct;216:18-24.

The aim of this study was to examine the effects of preoperative Carprofen on the cardiorespiratory, hormonal and metabolic stress response during umbilical surgery under isoflurane anaesthesia combined with local anaesthesia, in calves. A randomised, blinded experimental study was conducted in 24 calves. Carprofen (n = 12; 1.4 mg/kg) or physiological saline solution (controls; n = 12) was administered 1 h prior to surgery. Anaesthesia was induced with xylazine (0.1 mg/kg, IM) and, after the onset of sedation (i.e. after 5-8 min), ketamine was administered (2 mg/kg, IV). Anaesthesia was then maintained with isoflurane (ISO) in oxygen to effect and completed by infiltration of the incision line with 20 mL of 2% procaine. Cardiorespiratory, endocrine and metabolic parameters were examined before, during and after surgery at short intervals. In both groups, anaesthesia appeared adequate for the surgical intervention. Heart rate, stroke index and arterial blood pressure were significantly elevated after the onset of surgery. Oxygen partial pressure and oxygen delivery increased, while the oxygen extraction ratio decreased intraoperatively, ensuring sufficient oxygen supply. In the control group, the mean surge in serum cortisol concentrations tended to be higher (P = 0.089) and systemic vascular resistance (SVR) was significantly greater (P <0.05) than in the Carprofen group during surgery. In conclusion, the anaesthetic protocol used in this study induced reliable analgesia in both groups. The lower serum cortisol levels and SVR may indicate a reduced surgical stress response in calves undergoing umbilical surgery under ISO anaesthesia after administering Carprofen preoperatively.

Carprofen is a nonsteroid anti-inflammatory agent, acts as a multi-target FAAH/COX inhibitor, with IC50s of 3.9 μM, 22.3 μM and 78.6 μM for COX-2, COX-1 and FAAH, respectively.

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