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：...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 （Cmax） and area under the curve to the last sampling time （AUC0_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.展开更多
基金Liliana Zazueta-Beltran,Lorena Medina-Aymerich and Nadia Estela Diaz-Triste were supported by CONACYT fellowships
文摘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 （Cmax） and area under the curve to the last sampling time （AUC0_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.
