Abstract Title:

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

Abstract Source:

Int J Pharm. 2010 Oct 31;399(1-2):116-20. Epub 2010 Aug 18. PMID: 20727390

Abstract Author(s):

Yi-Dong Yan, Dae Hwan Kim, Jun Ho Sung, Chul Soon Yong, Han Gon Choi

Article Affiliation:

College of Pharmacy, Yeungnam University, Kyungsan, Kyungbuk, Republic of Korea.

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 i.v. route.

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