Life-threatening interaction between the root extract of Pueraria lobata and methotrexate in rats

Hsiu Mei Chiang; Shih Hua Fang; Kuo Ching Wen; Su Lan Hsiu; Shang Yuan Tsai; Yu Chi Hou; Ying Chang Chi; Pei Dawn Lee Chao

doi:10.1016/j.taap.2005.04.015

Life-threatening interaction between the root extract of Pueraria lobata and methotrexate in rats

Hsiu Mei Chiang, Shih Hua Fang, Kuo Ching Wen, Su Lan Hsiu, Shang Yuan Tsai, Yu Chi Hou, Ying Chang Chi, Pei Dawn Lee Chao^*

^*Corresponding author for this work

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

40 Scopus citations

Abstract

Isoflavone supplements are nowadays widely used as alternative for hormone replacement therapy. However, the safety remains unanswered. This study attempted to investigate the effect of Pueraria lobata root decoction (PLRD), an isoflavone-rich herb, on the pharmacokinetics of methotrexate (MTX), a bicarboxylate antimetabolite with narrow therapeutic window. Rats were orally and intravenously given methotrexate alone and coadministered with PLRD. Blood samples were withdrawn via cardiopuncture at specific time points after drug administration. Serum methotrexate concentrations were assayed by specific monoclonal fluorescence polarization immunoassay method. Pharmacokinetic parameters were calculated using noncompartment model of WINNONLIN for both oral and intravenous data of MTX. Our results showed that coadministration of 4.0 g/kg and 2.0 g/kg of PLRD significantly increased the AUC_0-t by 207.8% and 127.9%, prolonged the mean residence time (MRT) by 237.8 and 155.2%, respectively, finally resulted in surprisingly high mortalities of 57.1% and 14.3% in rats. When MTX was given intravenously, the coadministration of PLRD at 4.0 g/kg significantly increased the half-life by 53.9% and decreased the clearance by 47.9%. In conclusion, the coadministration of PLRD significantly decreased the elimination and resulted in markedly increased exposure of MTX in rats.

Original language	English
Pages (from-to)	263-268
Number of pages	6
Journal	Toxicology and Applied Pharmacology
Volume	209
Issue number	3
DOIs	https://doi.org/10.1016/j.taap.2005.04.015
State	Published - 15 12 2005
Externally published	Yes

Keywords

Isoflavone
Methotrexate
Multidrug resistance protein
Pueraria lobata

Access to Document

10.1016/j.taap.2005.04.015

Cite this

@article{b6caee1dc7f1401d8f35e3fc50a80846,

title = "Life-threatening interaction between the root extract of Pueraria lobata and methotrexate in rats",

abstract = "Isoflavone supplements are nowadays widely used as alternative for hormone replacement therapy. However, the safety remains unanswered. This study attempted to investigate the effect of Pueraria lobata root decoction (PLRD), an isoflavone-rich herb, on the pharmacokinetics of methotrexate (MTX), a bicarboxylate antimetabolite with narrow therapeutic window. Rats were orally and intravenously given methotrexate alone and coadministered with PLRD. Blood samples were withdrawn via cardiopuncture at specific time points after drug administration. Serum methotrexate concentrations were assayed by specific monoclonal fluorescence polarization immunoassay method. Pharmacokinetic parameters were calculated using noncompartment model of WINNONLIN for both oral and intravenous data of MTX. Our results showed that coadministration of 4.0 g/kg and 2.0 g/kg of PLRD significantly increased the AUC0-t by 207.8% and 127.9%, prolonged the mean residence time (MRT) by 237.8 and 155.2%, respectively, finally resulted in surprisingly high mortalities of 57.1% and 14.3% in rats. When MTX was given intravenously, the coadministration of PLRD at 4.0 g/kg significantly increased the half-life by 53.9% and decreased the clearance by 47.9%. In conclusion, the coadministration of PLRD significantly decreased the elimination and resulted in markedly increased exposure of MTX in rats.",

keywords = "Isoflavone, Methotrexate, Multidrug resistance protein, Pueraria lobata",

author = "Chiang, {Hsiu Mei} and Fang, {Shih Hua} and Wen, {Kuo Ching} and Hsiu, {Su Lan} and Tsai, {Shang Yuan} and Hou, {Yu Chi} and Chi, {Ying Chang} and {Lee Chao}, {Pei Dawn}",

year = "2005",

month = dec,

day = "15",

doi = "10.1016/j.taap.2005.04.015",

language = "英语",

volume = "209",

pages = "263--268",

journal = "Toxicology and Applied Pharmacology",

issn = "0041-008X",

publisher = "Academic Press Inc.",

number = "3",

}

TY - JOUR

T1 - Life-threatening interaction between the root extract of Pueraria lobata and methotrexate in rats

AU - Chiang, Hsiu Mei

AU - Fang, Shih Hua

AU - Wen, Kuo Ching

AU - Hsiu, Su Lan

AU - Tsai, Shang Yuan

AU - Hou, Yu Chi

AU - Chi, Ying Chang

AU - Lee Chao, Pei Dawn

PY - 2005/12/15

Y1 - 2005/12/15

N2 - Isoflavone supplements are nowadays widely used as alternative for hormone replacement therapy. However, the safety remains unanswered. This study attempted to investigate the effect of Pueraria lobata root decoction (PLRD), an isoflavone-rich herb, on the pharmacokinetics of methotrexate (MTX), a bicarboxylate antimetabolite with narrow therapeutic window. Rats were orally and intravenously given methotrexate alone and coadministered with PLRD. Blood samples were withdrawn via cardiopuncture at specific time points after drug administration. Serum methotrexate concentrations were assayed by specific monoclonal fluorescence polarization immunoassay method. Pharmacokinetic parameters were calculated using noncompartment model of WINNONLIN for both oral and intravenous data of MTX. Our results showed that coadministration of 4.0 g/kg and 2.0 g/kg of PLRD significantly increased the AUC0-t by 207.8% and 127.9%, prolonged the mean residence time (MRT) by 237.8 and 155.2%, respectively, finally resulted in surprisingly high mortalities of 57.1% and 14.3% in rats. When MTX was given intravenously, the coadministration of PLRD at 4.0 g/kg significantly increased the half-life by 53.9% and decreased the clearance by 47.9%. In conclusion, the coadministration of PLRD significantly decreased the elimination and resulted in markedly increased exposure of MTX in rats.

AB - Isoflavone supplements are nowadays widely used as alternative for hormone replacement therapy. However, the safety remains unanswered. This study attempted to investigate the effect of Pueraria lobata root decoction (PLRD), an isoflavone-rich herb, on the pharmacokinetics of methotrexate (MTX), a bicarboxylate antimetabolite with narrow therapeutic window. Rats were orally and intravenously given methotrexate alone and coadministered with PLRD. Blood samples were withdrawn via cardiopuncture at specific time points after drug administration. Serum methotrexate concentrations were assayed by specific monoclonal fluorescence polarization immunoassay method. Pharmacokinetic parameters were calculated using noncompartment model of WINNONLIN for both oral and intravenous data of MTX. Our results showed that coadministration of 4.0 g/kg and 2.0 g/kg of PLRD significantly increased the AUC0-t by 207.8% and 127.9%, prolonged the mean residence time (MRT) by 237.8 and 155.2%, respectively, finally resulted in surprisingly high mortalities of 57.1% and 14.3% in rats. When MTX was given intravenously, the coadministration of PLRD at 4.0 g/kg significantly increased the half-life by 53.9% and decreased the clearance by 47.9%. In conclusion, the coadministration of PLRD significantly decreased the elimination and resulted in markedly increased exposure of MTX in rats.

KW - Isoflavone

KW - Methotrexate

KW - Multidrug resistance protein

KW - Pueraria lobata

UR - http://www.scopus.com/inward/record.url?scp=28244438003&partnerID=8YFLogxK

U2 - 10.1016/j.taap.2005.04.015

DO - 10.1016/j.taap.2005.04.015

M3 - 文章

C2 - 15936791

AN - SCOPUS:28244438003

SN - 0041-008X

VL - 209

SP - 263

EP - 268

JO - Toxicology and Applied Pharmacology

JF - Toxicology and Applied Pharmacology

IS - 3

ER -

Life-threatening interaction between the root extract of Pueraria lobata and methotrexate in rats

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this