Enhanced bioavailability of paclitaxel after oral coadministration with flavone in rats.
The purpose of this study was to investigate the effect of flavone on the bioavailability of paclitaxel orally coadministered in rats. Paclitaxel (40 mg/kg) and flavone (2, 10, 20 mg/kg) were orally administered to rats orally. The plasma concentration of paclitaxel with flavone increased significantly (P < 0.01) compared to that of paclitaxel control. Area under the plasma concentration-time curve (AUC) of paclitaxel with the dose of 2-20 mg/kg flavone was significantly (P < 0.05 at 10 mg/kg, P < 0.01 at 20 mg/kg) higher than that of control. AUCs of paclitaxel were increased dose-dependently in the dose range of flavone. The absorption rate constant (Ka) of paclitaxel with the dose of 10-20 mg/kg flavone was significantly increased (P < 0.05 at 10 mg/kg, P < 0.01 at 20 mg/kg) compared to that of control. Peak concentration (Cmax) of paclitaxel with the dose of 10-20 mg/kg flavone were significantly increased (P < 0.05 at 10 mg/kg, P < 0.01 at 20 mg/kg) compared to that of control. Half-life (t(1/2)) of paclitaxel with the dose of 10-20 mg/kg flavone was significantly prolonged (P < 0.05 at 10 mg/kg, P < 0.01 at 20 mg/kg) compared to that of control. The relative bioavailability increased significantly by about 2.38- or 3.10-fold (P < 0.05 at 10 mg/kg, P < 0.01 at 20 mg/kg) compared to that of paclitaxel control. Based on these results, It might be considered that the bioavailability of paclitaxel coadministered with flavone was significantly enhanced by the both inhibition of cytochrome P-450 and the P-gp efflux pump in the intestinal mucosa. It could be possible to administer paclitaxel orally besides the established i.v. route.
Choi
Jun-Shik
JS
College of Pharmacy, Chosun University, 375 Susukdong, Dongku, Gwangju 501-759, South Korea.
Choi
Hoo-Kyun
HK
Shin
Sang-Chul
SC
D000277:Adjuvants, Pharmaceutic / Q000494:pharmacology*; D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D004305:Dose-Response Relationship, Drug; D047309:Flavones; D005419:Flavonoids / Q000494:pharmacology*; D007408:Intestinal Absorption / Q000187:drug effects*; D008297:Male; D017239:Paclitaxel / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D000277:Adjuvants, Pharmaceutic; D047309:Flavones; D005419:Flavonoids; D017239:Paclitaxel; C043562:flavone