Pharmacokinetic alteration of paclitaxel by ferulic acid derivative

Jaeok Lee; Song Wha Chae; Lianji Ma; So Yeon Lim; Sarah Alnajjar; Hea Young Park Choo; Hwa Jeong Lee; Sandy Jeong Rhie

doi:10.3390/pharmaceutics11110593

Pharmacokinetic alteration of paclitaxel by ferulic acid derivative

Jaeok Lee, Song Wha Chae, Lianji Ma, So Yeon Lim, Sarah Alnajjar, Hea Young Park Choo, Hwa Jeong Lee, Sandy Jeong Rhie

Department of Pharmaceutical Sciences

Research output: Contribution to journal › Article › peer-review

4 Scopus citations

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 AUC_inf 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.

Original language	English
Article number	593
Journal	Pharmaceutics
Volume	11
Issue number	11
DOIs	https://doi.org/10.3390/pharmaceutics11110593
State	Published - Nov 2019

Bibliographical note

Funding Information:
This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MEST) (2017R1A2B4007869). We thank Marilyn E. Morris (University of Buffalo, USA) for providing the MCF-7/ADR cell line.

Funding Information:
Funding: This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MEST) (2017R1A2B4007869).

Publisher Copyright:
© 2019 by the authors.

Keywords

Bioavailability
Elimination
Ferulic acid derivatives
P-glycoprotein
Paclitaxel
Pharmacokinetics

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title = "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.",

keywords = "Bioavailability, Elimination, Ferulic acid derivatives, P-glycoprotein, Paclitaxel, Pharmacokinetics",

author = "Jaeok Lee and Chae, {Song Wha} and Lianji Ma and Lim, {So Yeon} and Sarah Alnajjar and Choo, {Hea Young Park} and Lee, {Hwa Jeong} and Rhie, {Sandy Jeong}",

note = "Funding Information: This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MEST) (2017R1A2B4007869). We thank Marilyn E. Morris (University of Buffalo, USA) for providing the MCF-7/ADR cell line. Funding Information: Funding: This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MEST) (2017R1A2B4007869). Publisher Copyright: {\textcopyright} 2019 by the authors.",

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doi = "10.3390/pharmaceutics11110593",

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AU - Lee, Jaeok

AU - Chae, Song Wha

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AU - Lim, So Yeon

AU - Alnajjar, Sarah

AU - Choo, Hea Young Park

AU - Lee, Hwa Jeong

AU - Rhie, Sandy Jeong

N1 - Funding Information: This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MEST) (2017R1A2B4007869). We thank Marilyn E. Morris (University of Buffalo, USA) for providing the MCF-7/ADR cell line. Funding Information: Funding: This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MEST) (2017R1A2B4007869). Publisher Copyright: © 2019 by the authors.

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N2 - 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.

AB - 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.

KW - Bioavailability

KW - Elimination

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Pharmacokinetic alteration of paclitaxel by ferulic acid derivative

Abstract

Bibliographical note

Keywords

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