Effects of astragaloside IV on the pharmacokinetics of omeprazole in rats

Context: Omeprazole and astragaloside IV (AS-IV) are widely used for the treatment of gastric ulcers in China clinics. Objective: This study investigates the effects of AS-IV on the pharmacokinetics of omeprazole in rats. Materials and methods: The pharmacokinetics of orally administered omeprazole...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Wei Liu, Guozhi Liu, Jing Liu
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2019
Materias:	cyp3a4 herb–drug interaction p-gp Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/64ef642d39634c4a84b50f094dc3bda8
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:64ef642d39634c4a84b50f094dc3bda8
record_format	dspace
spelling	oai:doaj.org-article:64ef642d39634c4a84b50f094dc3bda82021-11-17T14:21:56ZEffects of astragaloside IV on the pharmacokinetics of omeprazole in rats1388-02091744-511610.1080/13880209.2019.1636828https://doaj.org/article/64ef642d39634c4a84b50f094dc3bda82019-01-01T00:00:00Zhttp://dx.doi.org/10.1080/13880209.2019.1636828https://doaj.org/toc/1388-0209https://doaj.org/toc/1744-5116Context: Omeprazole and astragaloside IV (AS-IV) are widely used for the treatment of gastric ulcers in China clinics. Objective: This study investigates the effects of AS-IV on the pharmacokinetics of omeprazole in rats. Materials and methods: The pharmacokinetics of orally administered omeprazole (2 mg/kg), with or without AS-IV (100 mg/kg/day for 7 days) pretreatment, were investigated in male Sprague-Dawley rats (two groups of six animals each) using LC–MS/MS. A Caco-2 cell transwell model and rat liver microsome incubation systems were also used to support the in vivo pharmacokinetic data and investigate its potential mechanism. Results: The results indicated that co-administration of AS-IV could decrease the systemic exposure of omeprazole significantly (p < 0.05), including AUC0–t (717.20 ± 177.63 vs. 1166.25 ± 186.65 ng h/mL) and Cmax (272.35 ± 25.81 vs. 366.34 ± 32.57 ng/mL). The t1/2 of omeprazole also decreased significantly (1.78 ± 0.15 vs. 2.23 ± 0.27 h, p < 0.05). The efflux ratio of omeprazole across the Caco-2 cell transwell model increased significantly from 1.73 to 2.67 (p < 0.05), and the metabolic stability of omeprazole was decreased from 42.6 ± 7.8 to 26.2 ± 5.1 min with the pretreatment of AS-IV (p < 0.05). Discussion and conclusions: AS-IV could decrease the systemic exposure of omeprazole in rats when AS-IV and omeprazole were co-administered, and it might exert these effects through decreasing the absorption of omeprazole by inducing P-gp, or through accelerating the metabolism of omeprazole in rat liver by inducing the activity of CYP3A4.Wei LiuGuozhi LiuJing LiuTaylor & Francis Grouparticlecyp3a4herb–drug interactionp-gpTherapeutics. PharmacologyRM1-950ENPharmaceutical Biology, Vol 57, Iss 1, Pp 449-452 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	cyp3a4 herb–drug interaction p-gp Therapeutics. Pharmacology RM1-950
spellingShingle	cyp3a4 herb–drug interaction p-gp Therapeutics. Pharmacology RM1-950 Wei Liu Guozhi Liu Jing Liu Effects of astragaloside IV on the pharmacokinetics of omeprazole in rats
description	Context: Omeprazole and astragaloside IV (AS-IV) are widely used for the treatment of gastric ulcers in China clinics. Objective: This study investigates the effects of AS-IV on the pharmacokinetics of omeprazole in rats. Materials and methods: The pharmacokinetics of orally administered omeprazole (2 mg/kg), with or without AS-IV (100 mg/kg/day for 7 days) pretreatment, were investigated in male Sprague-Dawley rats (two groups of six animals each) using LC–MS/MS. A Caco-2 cell transwell model and rat liver microsome incubation systems were also used to support the in vivo pharmacokinetic data and investigate its potential mechanism. Results: The results indicated that co-administration of AS-IV could decrease the systemic exposure of omeprazole significantly (p < 0.05), including AUC0–t (717.20 ± 177.63 vs. 1166.25 ± 186.65 ng h/mL) and Cmax (272.35 ± 25.81 vs. 366.34 ± 32.57 ng/mL). The t1/2 of omeprazole also decreased significantly (1.78 ± 0.15 vs. 2.23 ± 0.27 h, p < 0.05). The efflux ratio of omeprazole across the Caco-2 cell transwell model increased significantly from 1.73 to 2.67 (p < 0.05), and the metabolic stability of omeprazole was decreased from 42.6 ± 7.8 to 26.2 ± 5.1 min with the pretreatment of AS-IV (p < 0.05). Discussion and conclusions: AS-IV could decrease the systemic exposure of omeprazole in rats when AS-IV and omeprazole were co-administered, and it might exert these effects through decreasing the absorption of omeprazole by inducing P-gp, or through accelerating the metabolism of omeprazole in rat liver by inducing the activity of CYP3A4.
format	article
author	Wei Liu Guozhi Liu Jing Liu
author_facet	Wei Liu Guozhi Liu Jing Liu
author_sort	Wei Liu
title	Effects of astragaloside IV on the pharmacokinetics of omeprazole in rats
title_short	Effects of astragaloside IV on the pharmacokinetics of omeprazole in rats
title_full	Effects of astragaloside IV on the pharmacokinetics of omeprazole in rats
title_fullStr	Effects of astragaloside IV on the pharmacokinetics of omeprazole in rats
title_full_unstemmed	Effects of astragaloside IV on the pharmacokinetics of omeprazole in rats
title_sort	effects of astragaloside iv on the pharmacokinetics of omeprazole in rats
publisher	Taylor & Francis Group
publishDate	2019
url	https://doaj.org/article/64ef642d39634c4a84b50f094dc3bda8
work_keys_str_mv	AT weiliu effectsofastragalosideivonthepharmacokineticsofomeprazoleinrats AT guozhiliu effectsofastragalosideivonthepharmacokineticsofomeprazoleinrats AT jingliu effectsofastragalosideivonthepharmacokineticsofomeprazoleinrats
_version_	1718425486568194048

Effects of astragaloside IV on the pharmacokinetics of omeprazole in rats

Ejemplares similares