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

Shih Ying Yang; Shin Hun Juang; Shang Yuan Tsai; Pei Dawn Lee Chao; Yu Chi Hou

doi:10.1016/j.taap.2012.05.020

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

Shih Ying Yang, Shin Hun Juang, Shang Yuan Tsai, Pei Dawn Lee Chao, Yu Chi Hou^*

^*Corresponding author for this work

China Medical University Taichung

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

17 Scopus citations

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 Blood was withdrawn at specific time points and serum MTX concentrations were assayed by a specific monoclonal fluorescence polarization immunoassay method.The results showed that 300mg/kg of SJW significantly increased the AUC _0-t and C _max of MTX by 163% and 60%, respectively, and 150mg/kg of SJW significantly increased the AUC _0-t of MTX by 55%. In addition, diclofenac enhanced the C _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.

Original language	English
Pages (from-to)	39-43
Number of pages	5
Journal	Toxicology and Applied Pharmacology
Volume	263
Issue number	1
DOIs	https://doi.org/10.1016/j.taap.2012.05.020
State	Published - 15 08 2012
Externally published	Yes

Keywords

Hypericum perforatum
Methotrexate
Pharmacokinetics
St. John's wort

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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 Blood was withdrawn at specific time points and serum MTX concentrations were assayed by a specific monoclonal fluorescence polarization immunoassay method.The results showed that 300mg/kg of SJW significantly increased the AUC 0-t and C max of MTX by 163% and 60%, respectively, and 150mg/kg of SJW significantly increased the AUC 0-t of MTX by 55%. In addition, diclofenac enhanced the C 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.",

keywords = "Hypericum perforatum, Methotrexate, Pharmacokinetics, St. John's wort",

author = "Yang, {Shih Ying} and Juang, {Shin Hun} and Tsai, {Shang Yuan} and Chao, {Pei Dawn Lee} and Hou, {Yu Chi}",

year = "2012",

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doi = "10.1016/j.taap.2012.05.020",

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AU - Yang, Shih Ying

AU - Juang, Shin Hun

AU - Tsai, Shang Yuan

AU - Chao, Pei Dawn Lee

AU - Hou, Yu Chi

PY - 2012/8/15

Y1 - 2012/8/15

N2 - 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 300mg/kg of SJW significantly increased the AUC 0-t and C max of MTX by 163% and 60%, respectively, and 150mg/kg of SJW significantly increased the AUC 0-t of MTX by 55%. In addition, diclofenac enhanced the C 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.

AB - 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 300mg/kg of SJW significantly increased the AUC 0-t and C max of MTX by 163% and 60%, respectively, and 150mg/kg of SJW significantly increased the AUC 0-t of MTX by 55%. In addition, diclofenac enhanced the C 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.

KW - Hypericum perforatum

KW - Methotrexate

KW - Pharmacokinetics

KW - St. John's wort

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AN - SCOPUS:84864136699

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JO - Toxicology and Applied Pharmacology

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ER -

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

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