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Title: St. John's wort significantly increased the systemic exposure and toxicity of methotrexate in rats

Abstract

St. John's wort (SJW, Hypericum perforatum) is one of the popular nutraceuticals for treating depression. Methotrexate (MTX) is an immunosuppressant with narrow therapeutic window. This study investigated the effect of SJW on MTX pharmacokinetics in rats. Rats were orally given MTX alone and coadministered with 300 and 150 mg/kg of SJW, and 25 mg/kg of diclofenac, respectively. Blood was withdrawn at specific time points and serum MTX concentrations were assayed by a specific monoclonal fluorescence polarization immunoassay method. The results showed that 300 mg/kg of SJW significantly increased the AUC{sub 0−t} and C{sub max} of MTX by 163% and 60%, respectively, and 150 mg/kg of SJW significantly increased the AUC{sub 0−t} of MTX by 55%. In addition, diclofenac enhanced the C{sub max} of MTX by 110%. The mortality of rats treated with SJW was higher than that of controls. In conclusion, coadministration of SJW significantly increased the systemic exposure and toxicity of MTX. The combined use of MTX with SJW would need to be with caution. -- Highlights: ► St. John's wort significantly increased the AUC{sub 0−t} and C{sub max} of methotrexate. ► Coadministration of St. John's wort increased the exposure and toxicity of methotrexate. ► The combined use ofmore » methotrexate with St. John's wort will need to be with caution.« less

Authors:
 [1];  [1]; ;  [2];  [2]
  1. Graduate Institute of Pharmaceutical Chemistry, China Medical University, Taichung, Taiwan (China)
  2. School of Pharmacy, China Medical University, Taichung, Taiwan (China)
Publication Date:
OSTI Identifier:
22215879
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 263; Journal Issue: 1; Other Information: Copyright (c) 2012 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; BLOOD; CONCENTRATION RATIO; FLUORESCENCE; IMMUNOASSAY; METHOTREXATE; MORTALITY; RATS; TOXICITY

Citation Formats

Yang, Shih-Ying, Juang, Shin-Hun, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan, Tsai, Shang-Yuan, Chao, Pei-Dawn Lee, Hou, Yu-Chi, and Department of Medical Research, China Medical University Hospital, Taichung, Taiwan. St. John's wort significantly increased the systemic exposure and toxicity of methotrexate in rats. United States: N. p., 2012. Web. doi:10.1016/J.TAAP.2012.05.020.
Yang, Shih-Ying, Juang, Shin-Hun, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan, Tsai, Shang-Yuan, Chao, Pei-Dawn Lee, Hou, Yu-Chi, & Department of Medical Research, China Medical University Hospital, Taichung, Taiwan. St. John's wort significantly increased the systemic exposure and toxicity of methotrexate in rats. United States. https://doi.org/10.1016/J.TAAP.2012.05.020
Yang, Shih-Ying, Juang, Shin-Hun, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan, Tsai, Shang-Yuan, Chao, Pei-Dawn Lee, Hou, Yu-Chi, and Department of Medical Research, China Medical University Hospital, Taichung, Taiwan. 2012. "St. John's wort significantly increased the systemic exposure and toxicity of methotrexate in rats". United States. https://doi.org/10.1016/J.TAAP.2012.05.020.
@article{osti_22215879,
title = {St. John's wort significantly increased the systemic exposure and toxicity of methotrexate in rats},
author = {Yang, Shih-Ying and Juang, Shin-Hun and Department of Medical Research, China Medical University Hospital, Taichung, Taiwan and Tsai, Shang-Yuan and Chao, Pei-Dawn Lee and Hou, Yu-Chi and Department of Medical Research, China Medical University Hospital, Taichung, Taiwan},
abstractNote = {St. John's wort (SJW, Hypericum perforatum) is one of the popular nutraceuticals for treating depression. Methotrexate (MTX) is an immunosuppressant with narrow therapeutic window. This study investigated the effect of SJW on MTX pharmacokinetics in rats. Rats were orally given MTX alone and coadministered with 300 and 150 mg/kg of SJW, and 25 mg/kg of diclofenac, respectively. Blood was withdrawn at specific time points and serum MTX concentrations were assayed by a specific monoclonal fluorescence polarization immunoassay method. The results showed that 300 mg/kg of SJW significantly increased the AUC{sub 0−t} and C{sub max} of MTX by 163% and 60%, respectively, and 150 mg/kg of SJW significantly increased the AUC{sub 0−t} of MTX by 55%. In addition, diclofenac enhanced the C{sub max} of MTX by 110%. The mortality of rats treated with SJW was higher than that of controls. In conclusion, coadministration of SJW significantly increased the systemic exposure and toxicity of MTX. The combined use of MTX with SJW would need to be with caution. -- Highlights: ► St. John's wort significantly increased the AUC{sub 0−t} and C{sub max} of methotrexate. ► Coadministration of St. John's wort increased the exposure and toxicity of methotrexate. ► The combined use of methotrexate with St. John's wort will need to be with caution.},
doi = {10.1016/J.TAAP.2012.05.020},
url = {https://www.osti.gov/biblio/22215879}, journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = 1,
volume = 263,
place = {United States},
year = {Wed Aug 15 00:00:00 EDT 2012},
month = {Wed Aug 15 00:00:00 EDT 2012}
}