프라보노이드류인 모린과 나린진이 파크리탁셀의 생체이용률에 미치는 영향

Abstract

Paclitaxel has been used for effective chemotherapy for several types of neoplasms such as refractory breast cancer and ovarian cancer. This study was to investigate the effect of flavonoids on the bioavailability and pharmacokinetics of paclitaxel after oral and intravenous administration with flavonoids, morin and naringin, in rats. Blood samples were collected via femoral artery at 0, 0.1, 0.25, 0.5, 1, 2, 3, 4, 8, 12 and 24 hr after oral and intravenous administration. Plasma concentrations were determined by HPLC with UV detector. The plasma concentrations of paclitaxel pretreated with flavonoids (3.3 and 10 mg/kg) were increased significantly (p<0.05) compared to that of the control, given paclitaxel alonel. The plasma concentrations of paclitaxel coadministered with flavonoids were increased although it was not statistically signiticant compared to that of the control. Areas under the plasma concentration time curve (AUC) of paclitaxel pretreated with flavonoids were significantly (p<0.05) higher than that of control. The absorption rate constants (Ka) of paclitaxel pretreated with flavonoids were significantly increased compared to that of control. Peak concentrations (Cmax) of paclitaxel with flavonoids were significantly (p<0.05) increased compared to that of control. Absolute bioavailability (AB%) of paclitaxel pretreated with flavonoids was significantly (P<0.05) higher than that of control. AUC, Cmax, Ka and AB% of paclitaxel coadministered with flavonoids were increased, but there was no statisticalnot significance. following an intravenous administration of paclitaxel (3 mg/kg) with flavonoids such as morin and naringin (3.3 and 10 mg/kg), AUC and MRT were increased significantly (p<0.05) compared to those of control. Taken all together, the present study suggests that the altered pharmacokinetics of paclitaxel (by the concurrent use of flavonoids) might be due to both inhibition of metabolism and inhibition of P-glycoprotein efflux pump in the intestinal mucosa.