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 Cmax 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.

Plasma concentration–time curves of docetaxel in the rats assigned to the control, co-administered and treatment groups. Rats were treated with curcumin (100 mg/kg/day, p.o., treatment) or vehicle (10% Tween80, control, co-administerd) for four consecutive days. On day 5, the rats were gavaged with the vehicle (control) or 100 mg/kg curcumin (co-administered and with the vehicle (control)) or 100 mg/kg curcumin (co-administered and treatment group) 30 min before they were gavaged with 30 mg/kg docetaxel. Each value represents the mean ± S.D. (n = 5).Figure optionsDownload as PowerPoint slide