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Pharmacokinetic Alteration of Paclitaxel by Ferulic Acid Derivative.


ABSTRACT: P-glycoprotein (P-gp) is known to be involved in multidrug resistance (MDR) and modulation of pharmacokinetic (PK) profiles of substrate drugs. Here, we studied the effects of synthesized ferulic acid (FA) derivatives on P-gp function in vitro and examined PK alteration of paclitaxel (PTX), a well-known P-gp substrate drug by the derivative. Compound 5c, the FA derivative chosen as a significant P-gp inhibitor among eight FA candidates by in vitro results, increased PTX AUCinf as much as twofold versus the control by reducing PTX elimination in rats. These results suggest that FA derivative can increase PTX bioavailability by inhibiting P-gp existing in eliminating organs.

SUBMITTER: Lee J 

PROVIDER: S-EPMC6920777 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Pharmacokinetic Alteration of Paclitaxel by Ferulic Acid Derivative.

Lee Jaeok J   Chae Song Wha SW   Ma LianJi L   Lim So Yeon SY   Alnajjar Sarah S   Park Choo Hea-Young HY   Lee Hwa Jeong HJ   Rhie Sandy Jeong SJ  

Pharmaceutics 20191109 11


P-glycoprotein (P-gp) is known to be involved in multidrug resistance (MDR) and modulation of pharmacokinetic (PK) profiles of substrate drugs. Here, we studied the effects of synthesized ferulic acid (FA) derivatives on P-gp function in vitro and examined PK alteration of paclitaxel (PTX), a well-known P-gp substrate drug by the derivative. Compound <b>5c</b>, the FA derivative chosen as a significant P-gp inhibitor among eight FA candidates by in vitro results, increased PTX AUC<sub>inf</sub>  ...[more]

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