OBJECTIVE:To determine the role of a pharmacokinetic interaction in the protective effect of curcumin against the gastric damage induced by indomethacin administration as such or as its prodrug acemetacin.METHODS:Wistar rats orally received single dose of indomethacin(30 mg/kg) with and without curcumin(30 mg/kg);gastric injury was evaluated by determining the total damaged area.Additional groups of rats received an oral single dose of indomethacin(30 mg/kg) or its prodrug acemetacin(34.86 mg/kg) in the presence or absence of curcumin(30 mg/kg).Indomethacin and acemetacin concentrations in plasma from blood draws were determined by high-performance liquid chromatography.Plasma concentration-against-time curves were constructed,and bioavailability parameters,maximal concentration(C_(max)) and area under the curve to the last sampling time(AUC_(0-t)) were estimated.RESULTS:Concomitant administration of indomethacin and curcumin resulted in a significantly reduced gastric damage compared to indomethacin alone.However,co-administration of curcumin did not produce any significant alteration in the bioavailability parameters of indomethacin and acemetacin after administration of either the active compound or the prodrug.CONCLUSION:Curcumin exhibits a protective effect against indomethacin-induced gastric damage,but does not produce a reduction of the bioavailability of this nonsteroidal anti-inflammatory drug,indomethacin.Data thus suggest that a pharmacokinetic mechanism of action is not involved in curcumin gastroprotection. OBJECTIVE: To determine the role of a pharmacokinetic interaction in the protective effect of curcumin against the gastric damage induced by indomethacin administration as such or as its prodrug acemetacin. METHODS: Wistar rats orally received single dose of indomethacin (30 mg / kg) with and Without curcumin (30 mg / kg); gastric injury was evaluated by determining the total damaged area. Additional groups of rats received an oral single dose of indomethacin (30 mg / kg) or its prodrug acemetacin (34.86 mg / kg) in the presence or absence of curcumin (30 mg / kg) .Indomethacin and acemetacin concentrations in plasma from blood draws were determined by high-performance liquid chromatography. Plasma concentration-against-time curves were constructed, and bioavailability parameters, maximal concentration (C_ (max) ) and area under the curve to the last sampling time (AUC_ (0-t)) were estimated .RESULTS: Concomitant administration of indomethacin and curcumin resulted in a significantly reduced gastric damage to indomethacin alone. Despite, co-administration of curcumin did not produce any significant alteration in the bioavailability parameters of indomethacin and acemetacin after administration of either the active compound or the prodrug. CONCLUSION: Curcumin exhibits a protective effect against indomethacin-induced gastric damage, but does not produce a reduction of the bioavailability of this nonsteroidal anti-inflammatory drug, indomethacin. Data thus suggesting that a pharmacokinetic mechanism of action is not involved in curcumin gastroprotection.