Enhanced paclitaxel bioavailability after oral coadministration of paclitaxel prodrug with naringin to rats

The plasma concentrations of paclitaxel coadministered with naringin increased significantly (p < 0.01 at paclitaxel, p < 0.05 at prodrug) compared to the control. The areas under the plasma concentration-time curve (AUC) and the peak concentrations (Cmax) of paclitaxel with naringin significantly higher (p < 0.01) than the control. The half-life (t1/2) was significantly (p < 0.05) longer than the control. The absolute bioavailability (AB, %) of paclitaxel with naringin was significantly higher (3.5-6.8%, p < 0.01) than the control (2.2%). Absorption rate constant (Ka) of paclitaxel with naringin increased, but not significantly. The AUC of paclitaxel after coadministration of prodrug with naringin to rats was significantly (p < 0.05) higher than the prodrug control. The relative bioavailability (RB, %) of paclitaxel after coadministration of prodrug with naringin was 1.35-1.69-fold higher than prodrug control. The absolute bioavailability (AB, %) of paclitaxel after coadministration of prodrug with naringin increased significantly (p < 0.05) from 6.6 to 9.0% and 11.2%. The bioavailability of paclitaxel coadministered as a prodrug with or without naringin was remarkably higher than the control. Paclitaxel prodrug, a water-soluble compound concerning with its physicochemical properties, passes through the gastrointestinal mucosa more easily than paclitaxel without obstruction of P-gp and cytochrome P-450 in the gastrointestinal mucosa. Oral paclitaxel preparations which is more convenient than the IV dosage forms could be developed with a prodrug form with naringin.