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Wuzhi capsule increased systemic exposure to methotrexate by inhibiting the expression of OAT1/3 and P-gp

BACKGROUND: Methotrexate (MTX) is an important anticancer agent and immunosuppressant with a narrow therapeutic window. Wuzhi capsule (WZC) is an extract of Schisandra which is widely used to treat liver diseases. Co-administration of MTX and WZC is common in the clinical setting, but research on th...

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Autores principales: Fu, Ran, Wang, Xiao-Nan, Guo, Cai-Hui, Li, Ying, Ding, Cong-Yang, Li, Ya-Jing, Dong, Zhan-Jun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AME Publishing Company 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184478/
https://www.ncbi.nlm.nih.gov/pubmed/34164479
http://dx.doi.org/10.21037/atm-21-1303
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author Fu, Ran
Wang, Xiao-Nan
Guo, Cai-Hui
Li, Ying
Ding, Cong-Yang
Li, Ya-Jing
Dong, Zhan-Jun
author_facet Fu, Ran
Wang, Xiao-Nan
Guo, Cai-Hui
Li, Ying
Ding, Cong-Yang
Li, Ya-Jing
Dong, Zhan-Jun
author_sort Fu, Ran
collection PubMed
description BACKGROUND: Methotrexate (MTX) is an important anticancer agent and immunosuppressant with a narrow therapeutic window. Wuzhi capsule (WZC) is an extract of Schisandra which is widely used to treat liver diseases. Co-administration of MTX and WZC is common in the clinical setting, but research on the interaction between WZC and MTX is limited. This study aimed to investigate the effects of WZC on the pharmacokinetics of MTX in rats and to explore the role of membrane transport proteins OAT1/3 and P-gp in the interaction of these drugs. METHODS: Plasma MTX concentration was detected by ultra-performance liquid chromatography-tandem mass spectrometer (UPLC-MS/MS), and the messenger RNA (mRNA) and protein expression of OAT1/3 and P-gp was evaluated by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blotting analyses, respectively. RESULTS: The study results revealed that co-administration of WZC decreased the CL(z/F) and V(z/F) of MTX, increased the C(max) and area under the curve [(AUC)(0–24 h)] of MTX, and inhibited OAT1/3 expression in the kidney and P-gp expression in the small intestine. CONCLUSIONS: The findings suggested that there is a drug interaction between WZC and MTX and that OAT1/3 in the kidney and P-gp in the small intestine may be the main targets mediating the drug interaction, and attention should be paid when they are used in combination.
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spelling pubmed-81844782021-06-22 Wuzhi capsule increased systemic exposure to methotrexate by inhibiting the expression of OAT1/3 and P-gp Fu, Ran Wang, Xiao-Nan Guo, Cai-Hui Li, Ying Ding, Cong-Yang Li, Ya-Jing Dong, Zhan-Jun Ann Transl Med Original Article BACKGROUND: Methotrexate (MTX) is an important anticancer agent and immunosuppressant with a narrow therapeutic window. Wuzhi capsule (WZC) is an extract of Schisandra which is widely used to treat liver diseases. Co-administration of MTX and WZC is common in the clinical setting, but research on the interaction between WZC and MTX is limited. This study aimed to investigate the effects of WZC on the pharmacokinetics of MTX in rats and to explore the role of membrane transport proteins OAT1/3 and P-gp in the interaction of these drugs. METHODS: Plasma MTX concentration was detected by ultra-performance liquid chromatography-tandem mass spectrometer (UPLC-MS/MS), and the messenger RNA (mRNA) and protein expression of OAT1/3 and P-gp was evaluated by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blotting analyses, respectively. RESULTS: The study results revealed that co-administration of WZC decreased the CL(z/F) and V(z/F) of MTX, increased the C(max) and area under the curve [(AUC)(0–24 h)] of MTX, and inhibited OAT1/3 expression in the kidney and P-gp expression in the small intestine. CONCLUSIONS: The findings suggested that there is a drug interaction between WZC and MTX and that OAT1/3 in the kidney and P-gp in the small intestine may be the main targets mediating the drug interaction, and attention should be paid when they are used in combination. AME Publishing Company 2021-05 /pmc/articles/PMC8184478/ /pubmed/34164479 http://dx.doi.org/10.21037/atm-21-1303 Text en 2021 Annals of Translational Medicine. All rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Original Article
Fu, Ran
Wang, Xiao-Nan
Guo, Cai-Hui
Li, Ying
Ding, Cong-Yang
Li, Ya-Jing
Dong, Zhan-Jun
Wuzhi capsule increased systemic exposure to methotrexate by inhibiting the expression of OAT1/3 and P-gp
title Wuzhi capsule increased systemic exposure to methotrexate by inhibiting the expression of OAT1/3 and P-gp
title_full Wuzhi capsule increased systemic exposure to methotrexate by inhibiting the expression of OAT1/3 and P-gp
title_fullStr Wuzhi capsule increased systemic exposure to methotrexate by inhibiting the expression of OAT1/3 and P-gp
title_full_unstemmed Wuzhi capsule increased systemic exposure to methotrexate by inhibiting the expression of OAT1/3 and P-gp
title_short Wuzhi capsule increased systemic exposure to methotrexate by inhibiting the expression of OAT1/3 and P-gp
title_sort wuzhi capsule increased systemic exposure to methotrexate by inhibiting the expression of oat1/3 and p-gp
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184478/
https://www.ncbi.nlm.nih.gov/pubmed/34164479
http://dx.doi.org/10.21037/atm-21-1303
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