Enhancement of Paclitaxel Oral Bioavailability in Swiss Mice by Four Consecutive Days of Pre-Treatment with Curcumin

Abstract:

Objective: Poor water solubility, P-glycoprotein (P-gp) efflux property and substrate of CYP3A lead to low oral bioavailability that limit the oral use of paclitaxel, a key anticancer drug. Though several formulation approaches were tried to combat this low absorption profile but effect of pre-treatment with curcumin, a naturally occurring CYP3A and P-gp inhibitor on augmentation of paclitaxel plasma level is not reported till now. Therefore, the objective of the present study is to asses any change in oral pharmacokinetics of paclitaxel. Materials and Methods: curcumin was administered orally to the Swiss mice at a dose of 100 mg/kg for four days and on the fifth day, pharmacokinetics of paclitaxel was carried out at dose of 35 mg/kg orally alone and curcumin pre-treated animals. Results: There is enhancement of Cmax and AUC by 1.4 to 1.5 fold when compared with oral paclitaxel alone treatment that leads to improve in oral bioavailability of paclitaxel. Conclusion: Curcumin can be an ideal candidate for regular use to improve the bioavailability of paclitaxel followed by decrease in dose related side effects. Furthermore, anticancer effect of Curcumin itself as well as with paclitaxel could clinically manage cancer promisingly.

Key words: Paclitaxel, Curcumin, HPLC, Plasma, Pre-treatment, Bioavailability.