Enhanced oral bioavailability of docetaxel in rats by four consecutive days of pre-treatment with curcumin

Title
Enhanced oral bioavailability of docetaxel in rats by four consecutive days of pre-treatment with curcumin
Author(s)
용철순최한곤[최한곤]엄의동[엄의동]김대환[김대환]성준호[성준호]
Keywords
P-GLYCOPROTEIN; MULTIDRUG-RESISTANCE; IDENTIFICATION; ABSORPTION; PACLITAXEL; ENZYMES; DRUGS; TAXOL
Issue Date
201010
Publisher
ELSEVIER SCIENCE BV
Citation
INTERNATIONAL JOURNAL OF PHARMACEUTICS, v.399, no.1-2, pp.116 - 120
Abstract
As with many other anti-cancer agents, docetaxel is a substrate for ATP-binding cassette transporters such as P-glycoprotein and its metabolism is mainly catalysed by CYP3A. In order to improve the oral bioavailability of docetaxel, a component of turmeric, curcumin, which can down-regulate the intestinal P-glycoprotein and CYP3A protein levels, was used for the pre-treatment of rats before the oral administration of docetaxel. Curcumin (100 mg/kg) did not significantly modify the pharmacokinetics of docetaxel when given orally 30 min before the administration of docetaxel. However, the C(max) of docetaxel in rats pre-treated with curcumin for four consecutive days was significantly increased (p < 0.01) by about 10 times compared to that of the docetaxel control, and the area under the plasma concentration-time curve (AUC) was about eight times higher than that of the control. Consequently, the absolute bioavailability of docetaxel in the treatment group (four days of curcumin at 100 mg/kg) was about 40%, which was a significant increase of about eightfold in comparison to the control value. Thus, the oral bioavailability of docetaxel was enhanced by the co-administration of regular curcumin. It could be possible to administer docetaxel orally, besides the established iv. route. Crown Copyright (C) 2010 Published by Elsevier B.V. All rights reserved.
URI
http://hdl.handle.net/YU.REPOSITORY/23523http://dx.doi.org/10.1016/j.ijpharm.2010.08.015
ISSN
0378-5173
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약학대학 > 약학부 > Articles
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