Folium sennae increased the bioavailability of methotrexate through modulation on mrp 2 and bcrp

Chung Ping Yu; Yu Hsuan Peng; Ching Ya Huang; Yow Wen Hsieh; Yu Chi Hou; Shiuan Pey Lin

doi:10.3390/ph14101036

Folium sennae increased the bioavailability of methotrexate through modulation on mrp 2 and bcrp

Chung Ping Yu, Yu Hsuan Peng, Ching Ya Huang, Yow Wen Hsieh, Yu Chi Hou^*, Shiuan Pey Lin^*

^*Corresponding author for this work

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

2 Scopus citations

Abstract

Folium Sennae (FS), a popular laxative (Senna), contains polyphenolic anthranoids, whose conjugation metabolites are probable modulators of multidrug resistance-associated proteins (MRPs) and breast cancer resistance protein (BCRP). We suspected that the combined use of FS might alter the pharmacokinetics of various medicines transported by MRPs or BCRP. This study investigated the effect of FS on the pharmacokinetics of methotrexate (MTX), an anticancer drug and a probe substrate of MRPs/BCRP. Rats were orally administered MTX alone and with two dosage regimens of FS in a parallel design. The results show that 5.0 g/kg of FS significantly increased the AUC_0–2880, AUC_720–2880 and MRT of MTX by 45%, 102% and 42%, and the seventh dose of 2.5 g/kg of FS significantly enhanced the AUC_720–2880 and MRT by 78% and 42%, respectively. Mechanism studies indicated that the metabolites of FS (FSM) inhibited MRP 2 and BCRP. In conclusion, the combined use of FS increased the systemic exposure and MRT of MTX through inhibition on MRP 2 and BCRP.

Original language	English
Article number	1036
Journal	Pharmaceuticals
Volume	14
Issue number	10
DOIs	https://doi.org/10.3390/ph14101036
State	Published - 10 2021
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

Breast cancer resistance protein
Constipation
Folium sennae
Methotrexate
Multidrug resistance-associated proteins

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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title = "Folium sennae increased the bioavailability of methotrexate through modulation on mrp 2 and bcrp",

abstract = "Folium Sennae (FS), a popular laxative (Senna), contains polyphenolic anthranoids, whose conjugation metabolites are probable modulators of multidrug resistance-associated proteins (MRPs) and breast cancer resistance protein (BCRP). We suspected that the combined use of FS might alter the pharmacokinetics of various medicines transported by MRPs or BCRP. This study investigated the effect of FS on the pharmacokinetics of methotrexate (MTX), an anticancer drug and a probe substrate of MRPs/BCRP. Rats were orally administered MTX alone and with two dosage regimens of FS in a parallel design. The results show that 5.0 g/kg of FS significantly increased the AUC0–2880, AUC720–2880 and MRT of MTX by 45%, 102% and 42%, and the seventh dose of 2.5 g/kg of FS significantly enhanced the AUC720–2880 and MRT by 78% and 42%, respectively. Mechanism studies indicated that the metabolites of FS (FSM) inhibited MRP 2 and BCRP. In conclusion, the combined use of FS increased the systemic exposure and MRT of MTX through inhibition on MRP 2 and BCRP.",

keywords = "Breast cancer resistance protein, Constipation, Folium sennae, Methotrexate, Multidrug resistance-associated proteins",

author = "Yu, {Chung Ping} and Peng, {Yu Hsuan} and Huang, {Ching Ya} and Hsieh, {Yow Wen} and Hou, {Yu Chi} and Lin, {Shiuan Pey}",

note = "Publisher Copyright: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2021",

month = oct,

doi = "10.3390/ph14101036",

language = "英语",

volume = "14",

journal = "Pharmaceuticals",

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TY - JOUR

T1 - Folium sennae increased the bioavailability of methotrexate through modulation on mrp 2 and bcrp

AU - Yu, Chung Ping

AU - Peng, Yu Hsuan

AU - Huang, Ching Ya

AU - Hsieh, Yow Wen

AU - Hou, Yu Chi

AU - Lin, Shiuan Pey

PY - 2021/10

Y1 - 2021/10

N2 - Folium Sennae (FS), a popular laxative (Senna), contains polyphenolic anthranoids, whose conjugation metabolites are probable modulators of multidrug resistance-associated proteins (MRPs) and breast cancer resistance protein (BCRP). We suspected that the combined use of FS might alter the pharmacokinetics of various medicines transported by MRPs or BCRP. This study investigated the effect of FS on the pharmacokinetics of methotrexate (MTX), an anticancer drug and a probe substrate of MRPs/BCRP. Rats were orally administered MTX alone and with two dosage regimens of FS in a parallel design. The results show that 5.0 g/kg of FS significantly increased the AUC0–2880, AUC720–2880 and MRT of MTX by 45%, 102% and 42%, and the seventh dose of 2.5 g/kg of FS significantly enhanced the AUC720–2880 and MRT by 78% and 42%, respectively. Mechanism studies indicated that the metabolites of FS (FSM) inhibited MRP 2 and BCRP. In conclusion, the combined use of FS increased the systemic exposure and MRT of MTX through inhibition on MRP 2 and BCRP.

AB - Folium Sennae (FS), a popular laxative (Senna), contains polyphenolic anthranoids, whose conjugation metabolites are probable modulators of multidrug resistance-associated proteins (MRPs) and breast cancer resistance protein (BCRP). We suspected that the combined use of FS might alter the pharmacokinetics of various medicines transported by MRPs or BCRP. This study investigated the effect of FS on the pharmacokinetics of methotrexate (MTX), an anticancer drug and a probe substrate of MRPs/BCRP. Rats were orally administered MTX alone and with two dosage regimens of FS in a parallel design. The results show that 5.0 g/kg of FS significantly increased the AUC0–2880, AUC720–2880 and MRT of MTX by 45%, 102% and 42%, and the seventh dose of 2.5 g/kg of FS significantly enhanced the AUC720–2880 and MRT by 78% and 42%, respectively. Mechanism studies indicated that the metabolites of FS (FSM) inhibited MRP 2 and BCRP. In conclusion, the combined use of FS increased the systemic exposure and MRT of MTX through inhibition on MRP 2 and BCRP.

KW - Breast cancer resistance protein

KW - Constipation

KW - Folium sennae

KW - Methotrexate

KW - Multidrug resistance-associated proteins

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U2 - 10.3390/ph14101036

DO - 10.3390/ph14101036

M3 - 文章

AN - SCOPUS:85117565704

SN - 1424-8247

VL - 14

JO - Pharmaceuticals

JF - Pharmaceuticals

IS - 10

M1 - 1036

ER -

Folium sennae increased the bioavailability of methotrexate through modulation on mrp 2 and bcrp

Abstract

Bibliographical note

Keywords

UN SDGs

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