Biological and Pharmaceutical Bulletin
Online ISSN : 1347-5215
Print ISSN : 0918-6158
ISSN-L : 0918-6158
Biliary Excretion of Curcumin Is Mediated by Multidrug Resistance-Associated Protein 2
Joo Hyun LeeJu-Hee OhYoung-Joo Lee
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2012 Volume 35 Issue 5 Pages 777-780


Curcumin has a wide spectrum of pharmacological activities, including antioxidant, anti-inflammatory, antimicrobial, and anticancer properties. Recently, its potential as effective chemoprevention against cholangiocarcinoma, a highly malignant tumor of the bile duct with limited therapeutic options, was reported. The purpose of the present study was to investigate the contribution of multidrug resistance-associated protein 2 (Mrp2) to the biliary excretion of curcumin using Sprague-Dawley rats (SDR) and Eisai hyperbilirubinemic rats (EHBR). After intravenous administration of curcumin with a loading dose of 4.5 mg/kg, followed by a constant infusion of 18 mg/kg/h to the SDR and EHBR, the pharmacokinetic parameters of curcumin were estimated. In EHBR, the total area under the bile concentration–time curve from 0 to 80 min following curcumin administration was dramatically decreased (0.094%) compared to that in SDR. In addition, the plasma-to-bile and liver-to-bile clearances were both significantly decreased compared to SDR. These results provide the first evidence that Mrp2 mediates the biliary excretion of curcumin and thus may be a major factor in the control of exposure of curcumin to the bile duct. This study may be helpful to the potential use of curcumin as a treatment for bile duct cancer, and to understanding the genetic polymorphism of Mrp2 for clinical trials of curcumin.

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© 2012 The Pharmaceutical Society of Japan
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