Pharmacokinetic study on the interaction between succinic acid and irbesartan in rats and its potential mechanism

Context Succinic acid and irbesartan are commonly used drugs in cardiovascular disease treatment. The interaction might occur during their co-administration, which was still unclear. Objective To reveal the effect of succinic acid on the metabolism of irbesartan and its potential mechanism. Material...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Yongpeng Wang, Ruping Rui, Xiaoyan Zhang, Bin Sun
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2021
Materias:	cardiovascular disease drug–drug interaction cyp2c9 amber Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/b85959821d584688b6004bc9ae771af7
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:b85959821d584688b6004bc9ae771af7
record_format	dspace
spelling	oai:doaj.org-article:b85959821d584688b6004bc9ae771af72021-11-26T11:19:47ZPharmacokinetic study on the interaction between succinic acid and irbesartan in rats and its potential mechanism1388-02091744-511610.1080/13880209.2021.2002370https://doaj.org/article/b85959821d584688b6004bc9ae771af72021-01-01T00:00:00Zhttp://dx.doi.org/10.1080/13880209.2021.2002370https://doaj.org/toc/1388-0209https://doaj.org/toc/1744-5116Context Succinic acid and irbesartan are commonly used drugs in cardiovascular disease treatment. The interaction might occur during their co-administration, which was still unclear. Objective To reveal the effect of succinic acid on the metabolism of irbesartan and its potential mechanism. Materials and methods The Sprague-Dawley rats (n = 6) were treated with a single dose of 30 mg/kg irbesartan (control) or the co-administration with the pre-treatment of 200 mg/kg succinic acid for 7 d. The effect of succinic acid on the metabolic stability and the activity of CYP2C9 was evaluated in rat liver microsomes. Results Succinic acid increased the AUC (5328.71 ± 959.31 μg/L × h vs. 3340.23 ± 737.75 μg/L × h) and prolonged the half-life of irbesartan (from 12.79 ± 0.73 h to 20.59 ± 6.35 h). The Tmax (2.83 ± 0.75 h vs. 3.83 ± 1.10 h) and clearance rate (3.46 ± 1.13 L/h/kg vs. 6.91 ± 1.65 L/h/kg) of irbesartan was reduced by succinic acid. Consistently, succinic acid improved the metabolic stability (half-life from 23.32 ± 3.46 to 27.35 ± 2.15 min, intrinsic clearance rate from 59.43 ± 6.12 to 50.68 ± 5.64 μL/min/mg protein). Succinic acid was also found to inhibit the activity of CYP2C9 with the IC50 value of 13.87 μM. Discussion and conclusions Succinic acid increased the system exposure of irbesartan via inhibiting CYP2C9. The experiment design of this study also provides a reference for the further validation of this interaction in humans.Yongpeng WangRuping RuiXiaoyan ZhangBin SunTaylor & Francis Grouparticlecardiovascular diseasedrug–drug interactioncyp2c9amberTherapeutics. PharmacologyRM1-950ENPharmaceutical Biology, Vol 59, Iss 1, Pp 1619-1622 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	cardiovascular disease drug–drug interaction cyp2c9 amber Therapeutics. Pharmacology RM1-950
spellingShingle	cardiovascular disease drug–drug interaction cyp2c9 amber Therapeutics. Pharmacology RM1-950 Yongpeng Wang Ruping Rui Xiaoyan Zhang Bin Sun Pharmacokinetic study on the interaction between succinic acid and irbesartan in rats and its potential mechanism
description	Context Succinic acid and irbesartan are commonly used drugs in cardiovascular disease treatment. The interaction might occur during their co-administration, which was still unclear. Objective To reveal the effect of succinic acid on the metabolism of irbesartan and its potential mechanism. Materials and methods The Sprague-Dawley rats (n = 6) were treated with a single dose of 30 mg/kg irbesartan (control) or the co-administration with the pre-treatment of 200 mg/kg succinic acid for 7 d. The effect of succinic acid on the metabolic stability and the activity of CYP2C9 was evaluated in rat liver microsomes. Results Succinic acid increased the AUC (5328.71 ± 959.31 μg/L × h vs. 3340.23 ± 737.75 μg/L × h) and prolonged the half-life of irbesartan (from 12.79 ± 0.73 h to 20.59 ± 6.35 h). The Tmax (2.83 ± 0.75 h vs. 3.83 ± 1.10 h) and clearance rate (3.46 ± 1.13 L/h/kg vs. 6.91 ± 1.65 L/h/kg) of irbesartan was reduced by succinic acid. Consistently, succinic acid improved the metabolic stability (half-life from 23.32 ± 3.46 to 27.35 ± 2.15 min, intrinsic clearance rate from 59.43 ± 6.12 to 50.68 ± 5.64 μL/min/mg protein). Succinic acid was also found to inhibit the activity of CYP2C9 with the IC50 value of 13.87 μM. Discussion and conclusions Succinic acid increased the system exposure of irbesartan via inhibiting CYP2C9. The experiment design of this study also provides a reference for the further validation of this interaction in humans.
format	article
author	Yongpeng Wang Ruping Rui Xiaoyan Zhang Bin Sun
author_facet	Yongpeng Wang Ruping Rui Xiaoyan Zhang Bin Sun
author_sort	Yongpeng Wang
title	Pharmacokinetic study on the interaction between succinic acid and irbesartan in rats and its potential mechanism
title_short	Pharmacokinetic study on the interaction between succinic acid and irbesartan in rats and its potential mechanism
title_full	Pharmacokinetic study on the interaction between succinic acid and irbesartan in rats and its potential mechanism
title_fullStr	Pharmacokinetic study on the interaction between succinic acid and irbesartan in rats and its potential mechanism
title_full_unstemmed	Pharmacokinetic study on the interaction between succinic acid and irbesartan in rats and its potential mechanism
title_sort	pharmacokinetic study on the interaction between succinic acid and irbesartan in rats and its potential mechanism
publisher	Taylor & Francis Group
publishDate	2021
url	https://doaj.org/article/b85959821d584688b6004bc9ae771af7
work_keys_str_mv	AT yongpengwang pharmacokineticstudyontheinteractionbetweensuccinicacidandirbesartaninratsanditspotentialmechanism AT rupingrui pharmacokineticstudyontheinteractionbetweensuccinicacidandirbesartaninratsanditspotentialmechanism AT xiaoyanzhang pharmacokineticstudyontheinteractionbetweensuccinicacidandirbesartaninratsanditspotentialmechanism AT binsun pharmacokineticstudyontheinteractionbetweensuccinicacidandirbesartaninratsanditspotentialmechanism
_version_	1718409557567340544

Pharmacokinetic study on the interaction between succinic acid and irbesartan in rats and its potential mechanism

Ejemplares similares