Dramatic increase in hepatic and biliary curcumin exposure by modulation of its elimination pathway in rats.

摘要: Objectives Curcumin, a major component of the food spice turmeric (Curcuma longa), has multiple beneficial effects on diseases liver and bile duct. We have investigated whether modulation curcumin elimination pathway could increase its hepatic biliary exposure in rats. Methods Probenecid, an inhibitor metabolism excretion curcumin, was used as modulator. After intravenous administration at dose 18 mg/kg/h without (control) or with co-infusion probenecid (230 mg/kg/h) rats, pharmacokinetic parameters were estimated. Key findings Coadministration significantly increased total area under plasma (1.88-fold) (6.73-fold) concentration–time curves from 0 to 80 min relative those controls. The tissue-to-plasma concentration ratio also dramatically (69.3-fold) by probenecid. These results may be attributed dual inhibitory probenecid, greater extent, via glucuronidation, lesser multidrug resistance-associated protein 2. Conclusions The probenecid-mediated suggested that use combination drug regimens involving modulators innovative approach for therapeutic curcumin.