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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 Blood samples were withdrawn via cardiopuncture at specific time points after drug administration.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 AUC{sub 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.

Authors:
 [1];  [2];  [3];  [4];  [5];  [5];  [6];  [1];  [7]
  1. Institute of Pharmaceutical Chemistry, China Medical University, Taichung, Taiwan (China)
  2. (China)
  3. School of Medicine, China Medical University, Taichung, Taiwan (China)
  4. School of Cosmeceutics, China Medical University, Taichung, Taiwan (China)
  5. School of Pharmacy, China Medical University, Taichung, Taiwan (China)
  6. School of Chinese Medicine, China Medical University, Taichung, Taiwan (China)
  7. School of Pharmacy, China Medical University, Taichung, Taiwan (China). E-mail: pdlee@mail.cmu.edu.tw
Publication Date:
OSTI Identifier:
20783390
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 209; Journal Issue: 3; Other Information: DOI: 10.1016/j.taap.2005.04.015; PII: S0041-008X(05)00187-0; Copyright (c) 2005 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; BLOOD; CLEARANCE; FLUORESCENCE; HALF-LIFE; HERBS; HORMONES; IMMUNOASSAY; METHOTREXATE; MORTALITY; POLARIZATION; RATS; SAFETY

Citation Formats

Chiang, H.-M., Jen-Teh Junior College of Medicine, Nursing and Management, Miaoli, Taiwan, Fang, S.-H., Wen, K.-C., Hsiu, S.-L., Tsai, Shang-Yuan, Hou, Y.-C., Chi, Y.-C., and Lee Chao, Pei-Dawn. Life-threatening interaction between the root extract of Pueraria lobata and methotrexate in rats. United States: N. p., 2005. Web. doi:10.1016/j.taap.2005.04.015.
Chiang, H.-M., Jen-Teh Junior College of Medicine, Nursing and Management, Miaoli, Taiwan, Fang, S.-H., Wen, K.-C., Hsiu, S.-L., Tsai, Shang-Yuan, Hou, Y.-C., Chi, Y.-C., & Lee Chao, Pei-Dawn. Life-threatening interaction between the root extract of Pueraria lobata and methotrexate in rats. United States. doi:10.1016/j.taap.2005.04.015.
Chiang, H.-M., Jen-Teh Junior College of Medicine, Nursing and Management, Miaoli, Taiwan, Fang, S.-H., Wen, K.-C., Hsiu, S.-L., Tsai, Shang-Yuan, Hou, Y.-C., Chi, Y.-C., and Lee Chao, Pei-Dawn. Thu . "Life-threatening interaction between the root extract of Pueraria lobata and methotrexate in rats". United States. doi:10.1016/j.taap.2005.04.015.
@article{osti_20783390,
title = {Life-threatening interaction between the root extract of Pueraria lobata and methotrexate in rats},
author = {Chiang, H.-M. and Jen-Teh Junior College of Medicine, Nursing and Management, Miaoli, Taiwan and Fang, S.-H. and Wen, K.-C. and Hsiu, S.-L. and Tsai, Shang-Yuan and Hou, Y.-C. and Chi, Y.-C. and Lee Chao, Pei-Dawn},
abstractNote = {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{sub 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.},
doi = {10.1016/j.taap.2005.04.015},
journal = {Toxicology and Applied Pharmacology},
number = 3,
volume = 209,
place = {United States},
year = {Thu Dec 15 00:00:00 EST 2005},
month = {Thu Dec 15 00:00:00 EST 2005}
}