Enhanced oral bioavailability of docetaxel in rats by four consecutive days of pre-treatment with curcumin.
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.
Yan
Yi-Dong
YD
College of Pharmacy, Yeungnam University, Kyungsan, Kyungbuk, Republic of Korea.
Kim
Dae Hwan
DH
Sung
Jun Ho
JH
Yong
Chul Soon
CS
Choi
Han Gon
HG
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D003474:Curcumin / Q000494:pharmacology / Q000627:therapeutic use*; D065692:Cytochrome P-450 CYP3A Inhibitors; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D007275:Injections, Intravenous; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013379:Substrate Specificity; D043823:Taxoids / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D065692:Cytochrome P-450 CYP3A Inhibitors; D004791:Enzyme Inhibitors; D043823:Taxoids; D000077143:Docetaxel; D003474:Curcumin