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Pharmacokinetic study on the interaction between pachymic acid and bavachin and its potential mechanism

CONTEXT: Pachymic acid and bavachin are commonly used drugs in the therapy of lung cancer. OBJECTIVE: The co-administration of pachymic acid and bavachin was investigated to evaluate their potential drug-drug interaction. MATERIALS AND METHODS: The pharmacokinetics of bavachin (10 mg/kg) was studied...

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Autores principales: Zhang, Jie, Liu, Lu, Li, Hong, Zhang, Bin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8439242/
https://www.ncbi.nlm.nih.gov/pubmed/34517743
http://dx.doi.org/10.1080/13880209.2021.1942924
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author Zhang, Jie
Liu, Lu
Li, Hong
Zhang, Bin
author_facet Zhang, Jie
Liu, Lu
Li, Hong
Zhang, Bin
author_sort Zhang, Jie
collection PubMed
description CONTEXT: Pachymic acid and bavachin are commonly used drugs in the therapy of lung cancer. OBJECTIVE: The co-administration of pachymic acid and bavachin was investigated to evaluate their potential drug-drug interaction. MATERIALS AND METHODS: The pharmacokinetics of bavachin (10 mg/kg) was studied in male Sprague-Dawley (SD) rats in the presence of pachymic acid (5 mg/kg) (n = 6). The rats without pre-treatment of pachymic acid were set as the control and the pre-treatment of pachymic acid was conducted for 7 days before the administration of bavachin. The effect of pachymic acid on the activity of CYP2C9 was also estimated in rat liver microsomes with corresponding probe substrates. RESULTS: Pachymic acid influenced the pharmacokinetic profile of bavachin with the increased AUC (32.82 ± 4.61 vs. 19.43 ± 3.26 μg/L/h), the prolonged t(1/2) (3.21 ± 0.65 vs. 2.32 ± 0.28 h), and the decreased CLz/F (307.25 ± 44.35 vs. 523.81 ± 88.67 L/h/kg) in vivo. The metabolic stability of bavachin was enhanced by pachymic acid and the transport of bavachin was inhibited by pachymic acid. Pachymic acid was found to inhibit the activity of CYP2C9 with the IC(50) of 21.25 µM as well as the activity of P-gp. DISCUSSION AND CONCLUSION: The interaction between pachymic acid and bavachin results from the inhibition of CYP2C9 and P-gp. The dose of bavachin should be adjusted when combining with pachymic acid. The study design can be generalized to a broader study population with adjustment in the dose.
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spelling pubmed-84392422021-09-15 Pharmacokinetic study on the interaction between pachymic acid and bavachin and its potential mechanism Zhang, Jie Liu, Lu Li, Hong Zhang, Bin Pharm Biol Research Article CONTEXT: Pachymic acid and bavachin are commonly used drugs in the therapy of lung cancer. OBJECTIVE: The co-administration of pachymic acid and bavachin was investigated to evaluate their potential drug-drug interaction. MATERIALS AND METHODS: The pharmacokinetics of bavachin (10 mg/kg) was studied in male Sprague-Dawley (SD) rats in the presence of pachymic acid (5 mg/kg) (n = 6). The rats without pre-treatment of pachymic acid were set as the control and the pre-treatment of pachymic acid was conducted for 7 days before the administration of bavachin. The effect of pachymic acid on the activity of CYP2C9 was also estimated in rat liver microsomes with corresponding probe substrates. RESULTS: Pachymic acid influenced the pharmacokinetic profile of bavachin with the increased AUC (32.82 ± 4.61 vs. 19.43 ± 3.26 μg/L/h), the prolonged t(1/2) (3.21 ± 0.65 vs. 2.32 ± 0.28 h), and the decreased CLz/F (307.25 ± 44.35 vs. 523.81 ± 88.67 L/h/kg) in vivo. The metabolic stability of bavachin was enhanced by pachymic acid and the transport of bavachin was inhibited by pachymic acid. Pachymic acid was found to inhibit the activity of CYP2C9 with the IC(50) of 21.25 µM as well as the activity of P-gp. DISCUSSION AND CONCLUSION: The interaction between pachymic acid and bavachin results from the inhibition of CYP2C9 and P-gp. The dose of bavachin should be adjusted when combining with pachymic acid. The study design can be generalized to a broader study population with adjustment in the dose. Taylor & Francis 2021-09-13 /pmc/articles/PMC8439242/ /pubmed/34517743 http://dx.doi.org/10.1080/13880209.2021.1942924 Text en © 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Zhang, Jie
Liu, Lu
Li, Hong
Zhang, Bin
Pharmacokinetic study on the interaction between pachymic acid and bavachin and its potential mechanism
title Pharmacokinetic study on the interaction between pachymic acid and bavachin and its potential mechanism
title_full Pharmacokinetic study on the interaction between pachymic acid and bavachin and its potential mechanism
title_fullStr Pharmacokinetic study on the interaction between pachymic acid and bavachin and its potential mechanism
title_full_unstemmed Pharmacokinetic study on the interaction between pachymic acid and bavachin and its potential mechanism
title_short Pharmacokinetic study on the interaction between pachymic acid and bavachin and its potential mechanism
title_sort pharmacokinetic study on the interaction between pachymic acid and bavachin and its potential mechanism
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8439242/
https://www.ncbi.nlm.nih.gov/pubmed/34517743
http://dx.doi.org/10.1080/13880209.2021.1942924
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