The Effect of Tetramethoxyflavone on the Pharmacokinetics of Paclitaxel in Rats

테트라메톡시프라본이 파크리탁셀의 약물동태에 미치는 영향

  • Published : 2004.08.01

Abstract

The pharmacokinetics of orally administered paclitlxel (50 mg/kg) was studied in six rabbits after 1hr pretreatment (2.0 mg/kg and 10 mg/kg) of tetramethoxyflavone or coadministration of (2.0 mg/kg, 10 mg/kg and 20 mg/kg) tetramethoxyflavone. The area under the plasma concentration-tine curve (AUC) and plasma concentration of paclitaxe1 coadministered with tetramethoxyflavone (10 mglkg) 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 (C$_{max}$) 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 P450 or P-glycoprotein efflux pump which are engaged in paclitaxel metabolism, result in increased AUC and t$_{1}$2/ of paclitaxel. However, further study should be conducted to clarify the roles of cytochrome P450 and P-glycoprotein on paclitaxel bioavailability with/or without tetramethoxyflavone. P-glycoprotein on paclitaxel bioavailability with/or without tetramethoxyflavone.

Keywords

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