Journal
JOURNAL OF PHARMACEUTICAL SCIENCES
Volume 105, Issue 1, Pages 343-349Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.xphs.2015.11.031
Keywords
methotrexate; scutellariae radix; herb-drug interaction; MRP2; BCRP
Funding
- Ministry of Science and Technology, Taiwan, ROC [MOST 103-2320-B-039-025, NSC 102-2320-B-039-014-MY2]
- China Medical University, Taiwan, ROC [CMU 103-N-01]
- China Medical University Hospital, Taiwan, ROC [DMR-104-093, DMR-104-094]
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Scutellariae radix (SR, roots of Scutellaria baicalensis Georgi), a popular Chinese medicine, contains plenty of flavonoids such as baicalin, wogonoside, baicalein, and wogonin. Methotrexate (MTX), an important immunosuppressant with a narrow therapeutic index, is a substrate of multidrug resistance-associated proteins (MRPs) and breast cancer resistance protein (BCRP). This study investigated the effect of SR on MTX pharmacokinetics and the underlying mechanisms. Rats were orally administered MTX alone and with 1.0 or 2.0 g/kg of SR. The serum concentrations of MTX were determined by a fluorescence polarization immunoassay. Cell models were used to explore the involvement of MRP2 and BCRP in the interaction. The results showed that 1.0 g/kg of SR significantly increased C-max, AUC(0-30), AUC(0-2880), and mean residence time (MRT) of MTX by 50%, 45%, 501%, and 347%, respectively, and 2.0 g/kg of SR significantly enhanced the AUC(0-2880) and MRT by 242% and 293%, respectively, but decreased AUC0-30 by 41%. Cell line studies indicated that SR activated the BCRP-mediated efflux transport, whereas the serum metabolites of SR inhibited both the BCRP-and MRP2-mediated efflux transports. In conclusion, SR ingestion increased the systemic exposure and MRT of MTX via modulation on MRP2 and BCRP. (C) 2016 American Pharmacists Association(R). Published by Elsevier Inc. All rights reserved.
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