Aqueous Stability and Oral Pharmacokinetics of Meloxicam and Carprofen in Male C57BL/6 Mice

We found that carprofen and meloxicam under 3 environmental conditions (ambient dark, ambient light, and 4 degrees C) remained stable for at least 7 d. We then evaluated the oral pharmacokinetics of meloxicam (20 mg/kg) and carprofen (10 mg/kg) in male C57BL/6 mice after oral gavage or administration in the drinking water. Mice did not drink meloxicam-medicated water but readily consumed carprofen-medicated water, consuming an average of 14.19 mL carprofen-medicated water per 100 g body weight daily; mice drank more during the dark phase than during the light phase. Plasma analyzed by HPLC (meloxicam) and tandem mass spectrometry (carprofen) revealed that the peak meloxicam and carprofen concentrations were 16.7 and 20.3 mu g/mL and occurred at 4 and 2 h after oral gavage, respectively. Similar blood levels were achieved after 12 h access to the carprofen-medicated water bottle. At 24 h after oral gavage, the drugs were not detectable in plasma. Meloxicam plasma AUC, elimination half-life, apparent volume of distribution, and apparent oral clearance were 160.4 mg/L x h, 7.4 h, 0.36 L/kg, and 0.125 mL/h x kg, respectively. Carprofen plasma AUC, elimination half-life, apparent volume of distribution, and apparent oral clearance were 160.8 mg/L x h, 7.4 h, 0.42 L/kg, and 0.062 mL/h x kg, respectively. No gross or microscopic evidence of toxicity was seen in any mouse. Our findings indicate that carprofen can be administered in drinking water to mice and that medicated water bottles should be placed 12 to 24 h prior to painful procedures.