A Pharmacokinetic and Analgesic Efficacy Study of Carprofen in Female CD1 Mice

• Published in: Journal of the American Association for Laboratory Animal Science Vol. 62; no. 6; pp. 545 - 552
• Main Authors: McKenna, Brandon A, Weaver, Hannah L, Kim, Jeffrey, Bowman, Madelyn W, Knych, Heather K, Kendall, Lon V
• Format: Journal Article
• Language: English
• Published: United States American Association for Laboratory Animal Science 11-11-2023
• Subjects: Analgesia - methods; Analgesia - veterinary; Analgesics - therapeutic use; Animals; Anti-Inflammatory Agents, Non-Steroidal; Carbazoles - therapeutic use; Female; Mice; Original Research; Pain, Postoperative - drug therapy; Pain, Postoperative - veterinary; Rodent Diseases - drug therapy
• ISSN: 1559-6109; 2769-6677
• DOI: 10.30802/AALAS-JAALAS-23-000041

The minimization of pain in research animals is a scientific and ethical necessity. Carprofen is commonly used for painmanagement in mice; however, some data suggest that the standard dosage of 5 mg/kg may not provide adequate analgesiaafter surgery. We hypothesized that a higher dose of carprofen in mice would reduce pain-associated behaviors and improveanalgesia without toxic effects. A pharmacokinetic study was performed in mice given carprofen subcutaneously at 10 or20 mg/kg. Plasma concentrations were measured at 0.25, 0.5, 1, 2, 4, 8, 12, 24, and 48 h after dosing ( n = 3 per time point andtreatment). At these doses, plasma levels were above the purported therapeutic level for at least 12 and 24 h, respectively,with respective half-lives of 14.9 and 10.2 h. For the efficacy study, 10 mice per group received anesthesia with or without anovariectomy. Mice were then given 5 or 10 mg/kg of carprofen, or saline subcutaneously every 12 h. Orbital tightening, archedposture, wound licking, rearing, grooming, nesting behavior, and activity were assessed before surgery and at 4, 8, 12, 24,and 48 h after surgery. The von Frey responses were assessed before and at 4, 12, 24, and 48 h after surgery. The efficacy studyshowed that all surgery groups had significantly higher scores for orbital tightening, arched posture, and wound lickingthan did the anesthesia-only groups at 4, 8, 12, and 24-h time points. At the 8 h time point, the surgery groups treated withcarprofen had significantly lower arched posture scores than did the surgery group treated with saline only. No significantdifferences were found between carprofen treatment groups for rearing, grooming, von Frey, activity, or nesting behavior atany time point. These results indicate that subcutaneous carprofen administered at these doses does not provide sufficientanalgesia to alleviate postoperative pain in female CD1 mice.