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.
Bibliographical noteFunding 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: This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MEST) (2017R1A2B4007869).
© 2019 by the authors.
- Ferulic acid derivatives