Indomethacin-ethanol interactions on acute inflammation.

The effect of ethanol on the anti-inflammatory actions of indomethacin was studied using carrageenan-induced edema in the paw of the rat as the test for acute inflammation. The agents were administered 1 hour prior to carrageenan injection, and the volume of the paw was measured immediately and at 3 and 5 hours after carrageenan. Ethanol at 1, 2, and 4 g/kg and indomethacin at 5 and 20 mg/kg significantly inhibited paw edema at 3 and 5 hours. The combination of the various doses of ethanol and indomethacin produced the same degree of inhibition as ethanol alone and significantly higher inhibition than indomethacin alone. The concentration of indomethacin in the inflammed paw was significantly higher than in the other paw in animals receiving 20 mg/kg indomethacin alone and 5 or 20 mg/kg indomethacin in combination with 2 g/kg ethanol. Ethanol co-administration significantly increased the concentration of indomethacin in the inflammed paw. Whether the observed interaction is due to increased concentration of indomethacin at the site of action or to direct interaction of ethanol and indomethacin in the inflammation process remains unclear.