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The Pharmacokinetics and Clinical Efficacy of Oral Carprofen in the Laboratory Mouse

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Title: The Pharmacokinetics and Clinical Efficacy of Oral Carprofen in the Laboratory Mouse
Author: Ingrao, Joelle
Department: Department of Pathobiology
Program: Pathobiology
Advisor: Foster, Robert
Abstract: Provision of analgesia to laboratory mice can be challenging, and administration of analgesics via the water bottle is attractive in that it diminishes the time, training, skill, animal stress, and costs associated with other methods. The current study aimed to determine whether carprofen could be administered to mice via the drinking water by assessing stability, palatability, and clinical efficacy following ovariectomy. We demonstrated that both injectable meloxicam and carprofen are stable for 7 d in ambient light at room temperature, in dark at room temperature, and in dark at 4 °C. Carprofen is palatable to mice when administered via the drinking water, whereas meloxicam-medicated water is non-palatable. Mice drink an average of 18.4 mL of carprofen-medicated water / 100 g body weight / 24 h, and drink more in the dark phase compared to the light. Following a single oral gavage of 10 mg/kg carprofen, peak plasma concentration (20.3 +/- 2.4 μg/mL) occurs at 2 h post-administration. With access to a carprofen-medicated water bottle (10 mg/kg, 0.067 mg/mL), a comparable peak plasma concentration (17.0 +/- 2.9 μg/ml) is achieved following 12 to 24 h exposure. In order to assess clinical efficacy, mice received 10 or 20 mg/kg carprofen subcutaneously (immediately postoperative) or gained access to a carprofen-medicated water bottle for 24 h prior to ovariectomy. No significant behavioural changes were detected between treatment groups postoperatively. Following ovariectomy, pain was detected up to 1 h postoperatively, using facial grimacing as an indicator of pain. In comparison to control mice that did not undergo anesthesia or surgery, grimacing was reduced in duration in mice receiving 10 or 20 mg/kg carprofen subcutaneously or orally. However, no overall statistically significant difference could be detected between treatment groups using the Mouse Grimace Scale. Administration of 20 mg/kg carprofen subcutaneously or orally resulted in no significant difference in behavioural changes or facial grimacing compared to saline administration, which may be in part due to insufficient dose. The current study emphasizes the need for further evaluation of the clinical efficacy of nonsteroidal anti-inflammatory doses in mice prior to administration. Administration of carprofen via the water may be a feasible and efficacious method to administer analgesics to laboratory mice; however, further studies are required to determine optimal doses to achieve sufficient analgesia, particularly across a wide range of painful procedures.
Date: 2014-09
Rights: Attribution-NonCommercial-NoDerivs 2.5 Canada
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Attribution-NonCommercial-NoDerivs 2.5 Canada Except where otherwise noted, this item's license is described as Attribution-NonCommercial-NoDerivs 2.5 Canada