테트라메톡시프라본이 파크리탁셀의 약물동태에 미치는 영향

The Effect of Tetramethoxyflavone on the Pharmacokinetics of Paclitaxel in Rats

The pharmacokinetics of orally administered paclitaxel (50 mg/kg) was studied in six rabbits after 1hr pretreatment (2.0 mg/kg and 10 mg/kg) of tetramethoxyflavone or coadminlstration of (2.0 mg/kg, 10 mg/kg and 20 mg/kg) tetramethoxyflavone. The area under the plasma concentration-time curve (AUC) and plasma concentration of paclitaxel coadministered with tetramethoxyflavone (10 mg/kg) were increased significantly (p<0.05) compared with control. However, coadministration of tetramethoxyflavone (2 and 20 mg/kg) showed no significant effect on the pharmacokinetic parameters of paclitaxel. Pretreatment with tetramethoxyflavone significantly (p<0.05) increased the plasma concentration of paclitaxel. The area under the plasma concentration-time curve (AUC) and the peak concentration (Cmax) of paclitaxel pretreated with tetramethoxyflavone were Increased significantly (p<0.01, p <0.05) compared with control. The terminal half-life of paclitaxel pretreated with tetramethoxyflavone (2 mg/kg and 10 mg/kg) was significantly (p <0.05) prolonged compared with control. Pretreatment with tetramethoxyflavone (2.0 mg/kg, 10 mg/kg) significantly (p<0.01, p<0.05) increased the absolute bioavailability of paclitaxel compared with the control (154~179%). On the basis of the results, it might be considered that tetramethoxyflavone may inhibit cytochrome P45O or P-glycoprotein efflux pump which are engaged in paclitaxel metabolism, result in increased AUC and t1/2 of paclitaxel. However, further study should be conducted to clarify the roles of cytochrome P45O and P-glycoprotein on paclitaxel bioavailability witvor without tetramethoxyflavone.