Chung-Ping Yu, School of Pharmacy, College of Pharmacy, China Medical University, Taichung, Taiwan 406040, ROC.
Pei-Ying Li, School of Pharmacy, College of Pharmacy, China Medical University, Taichung, Taiwan 406040, ROC.
Szu-Yu Chen, School of Pharmacy, College of Pharmacy, China Medical University, Taichung, Taiwan 406040, ROC.
Shiuan-Pey Lin, School of Pharmacy, College of Pharmacy, China Medical University, Taichung, Taiwan 406040, ROC.
Ying-Chen Chen, Institute of Chinese Pharmaceutical Sciences, China Medical University, Taichung, Taiwan 404333, ROC.
Lu-Ching Ho, Department of Pharmacy, China Medical University Hospital, Taichung, Taiwan 404327, ROC.
Yow-Wen Hsieh, Department of Pharmacy, China Medical University Hospital, Taichung, Taiwan 404327, ROC.
Yu-Chi Hou, School of Pharmacy, College of Pharmacy, China Medical University, Taichung, Taiwan 406040, ROC.Follow

Magnoliae Officinalis Cortex (MOC), an herbal drug, contains polyphenolic lignans mainly magnolol (MN) and honokiol (HK). Methotrexate (MTX), a critical drug for cancers and autoimmune deseases, is a substrate of multidrug resistance-associated protein 2 (MRP2) and breast cancer resistance protein (BCRP). This study investigated the effect of coadministration of MOC on the pharmacokinetics of MTX and relevant mechanisms. Sprague-Dawley rats were orally administered MTX alone and with single dose (2.0 and 4.0 g/kg) and repeated seven doses of MOC (2.0 g/kg thrice daily for 2 days, the 7th dose given at 0.5 h before MTX). The serum concentrations of MTX were determined by a fluorescence polarization immunoassay. The results showed that a single dose of MOC at 2.0 g/kg significantly increased the AUC0-t and MRT of MTX by 352% and 308%, and a single dose at 4.0 g/kg significantly enhanced the AUC0-t and MRT by 362% and 291%, respectively. Likewise, repeated seven doses of MOC at 2.0 g/kg significantly increased the AUC0-t and MRT of MTX by 461% and 334%, respectively. Mechanism studies indicated that the function of MRP2 was significantly inhibited by MN, HK and the serum metabolites of MOC (MOCM), whereas BCRP was not inhibited by MOCM. In conclusion, coadministration of MOC markedly enhanced the systemic exposure and mean residence time of MTX through inhibiting the MRP2-mediated excretion of MTX.

Yu, Chung-Ping; Li, Pei-Ying; Chen, Szu-Yu; Lin, Shiuan-Pey; Chen, Ying-Chen; Ho, Lu-Ching; Hsieh, Yow-Wen; and Hou, Yu-Chi (2024) "An acute herb-drug interaction of Magnoliae Officinalis Cortex with methotrexate via inhibiting multidrug resistance-associated protein 2," Journal of Food and Drug Analysis: Vol. 32 : Iss. 1 , Article 7.
Available at: https://doi.org/10.38212/2224-6614.3495

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