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Pharmacokinetic interaction study between ligustrazine and valsartan in rats and its potential mechanism

CONTEXT: Ligustrazine and valsartan are commonly used drugs in the treatment of cardiac and cardiovascular disease. OBJECTIVE: The interaction between ligustrazine and valsartan was studied to investigate the effect of ligustrazine on the pharmacokinetics of valsartan. MATERIALS AND METHODS: The pha...

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Autores principales: Liu, Yang, Zhang, Jiaqi, Wu, Di, Cui, Liran
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7759250/
https://www.ncbi.nlm.nih.gov/pubmed/33355495
http://dx.doi.org/10.1080/13880209.2020.1859554
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author Liu, Yang
Zhang, Jiaqi
Wu, Di
Cui, Liran
author_facet Liu, Yang
Zhang, Jiaqi
Wu, Di
Cui, Liran
author_sort Liu, Yang
collection PubMed
description CONTEXT: Ligustrazine and valsartan are commonly used drugs in the treatment of cardiac and cardiovascular disease. OBJECTIVE: The interaction between ligustrazine and valsartan was studied to investigate the effect of ligustrazine on the pharmacokinetics of valsartan. MATERIALS AND METHODS: The pharmacokinetics of valsartan (10 mg/kg) was investigated in Sprague–Dawley rats divided into three groups (with the pretreatment of 4 or 10 mg/kg/day ligustrazine for 10 days and without the pretreatment of ligustrazine as control) of six rats each. The in vitro experiments in rat liver microsomes were performed to explore the effect of ligustrazine on the metabolic stability of valsartan. RESULTS: Ligustrazine changed the pharmacokinetic profile of valsartan. In the presence of 4 mg/kg ligustrazine, the AUC((0–)(t)()) (385.37 ± 93.05 versus 851.64 ± 104.26 μg/L*h), t(1/2) (5.46 ± 0.93 versus 6.34 ± 1.25 h), and C(max) (62.64 ± 9.09 versus 83.87 ± 6.15 μg/L) of valsartan was significantly decreased, and the clearance rate was increased from 10.92 ± 1.521 to 25.76 ± 6.24 L/h/kg and similar changes were observed in the group with 10 mg/kg ligustrazine (p < 0.05). The metabolic stability of valsartan was also decreased by ligustrazine as the half-life of valsartan in rat liver microsomes decreased from 37.12 ± 4.06 to 33.48 ± 3.56 min and the intrinsic clearance rate increased from 37.34 ± 3.84 to 41.40 ± 4.32 μL/min/mg protein (p < 0.05). DISCUSSION AND CONCLUSIONS: Ligustrazine promoted the metabolism of valsartan via activating CYP3A4. The co-administration of ligustrazine and valsartan should be taken into account.
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spelling pubmed-77592502021-01-08 Pharmacokinetic interaction study between ligustrazine and valsartan in rats and its potential mechanism Liu, Yang Zhang, Jiaqi Wu, Di Cui, Liran Pharm Biol Research Article CONTEXT: Ligustrazine and valsartan are commonly used drugs in the treatment of cardiac and cardiovascular disease. OBJECTIVE: The interaction between ligustrazine and valsartan was studied to investigate the effect of ligustrazine on the pharmacokinetics of valsartan. MATERIALS AND METHODS: The pharmacokinetics of valsartan (10 mg/kg) was investigated in Sprague–Dawley rats divided into three groups (with the pretreatment of 4 or 10 mg/kg/day ligustrazine for 10 days and without the pretreatment of ligustrazine as control) of six rats each. The in vitro experiments in rat liver microsomes were performed to explore the effect of ligustrazine on the metabolic stability of valsartan. RESULTS: Ligustrazine changed the pharmacokinetic profile of valsartan. In the presence of 4 mg/kg ligustrazine, the AUC((0–)(t)()) (385.37 ± 93.05 versus 851.64 ± 104.26 μg/L*h), t(1/2) (5.46 ± 0.93 versus 6.34 ± 1.25 h), and C(max) (62.64 ± 9.09 versus 83.87 ± 6.15 μg/L) of valsartan was significantly decreased, and the clearance rate was increased from 10.92 ± 1.521 to 25.76 ± 6.24 L/h/kg and similar changes were observed in the group with 10 mg/kg ligustrazine (p < 0.05). The metabolic stability of valsartan was also decreased by ligustrazine as the half-life of valsartan in rat liver microsomes decreased from 37.12 ± 4.06 to 33.48 ± 3.56 min and the intrinsic clearance rate increased from 37.34 ± 3.84 to 41.40 ± 4.32 μL/min/mg protein (p < 0.05). DISCUSSION AND CONCLUSIONS: Ligustrazine promoted the metabolism of valsartan via activating CYP3A4. The co-administration of ligustrazine and valsartan should be taken into account. Taylor & Francis 2020-12-23 /pmc/articles/PMC7759250/ /pubmed/33355495 http://dx.doi.org/10.1080/13880209.2020.1859554 Text en © 2020 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
Liu, Yang
Zhang, Jiaqi
Wu, Di
Cui, Liran
Pharmacokinetic interaction study between ligustrazine and valsartan in rats and its potential mechanism
title Pharmacokinetic interaction study between ligustrazine and valsartan in rats and its potential mechanism
title_full Pharmacokinetic interaction study between ligustrazine and valsartan in rats and its potential mechanism
title_fullStr Pharmacokinetic interaction study between ligustrazine and valsartan in rats and its potential mechanism
title_full_unstemmed Pharmacokinetic interaction study between ligustrazine and valsartan in rats and its potential mechanism
title_short Pharmacokinetic interaction study between ligustrazine and valsartan in rats and its potential mechanism
title_sort pharmacokinetic interaction study between ligustrazine and valsartan in rats and its potential mechanism
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7759250/
https://www.ncbi.nlm.nih.gov/pubmed/33355495
http://dx.doi.org/10.1080/13880209.2020.1859554
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