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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...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6691885/ https://www.ncbi.nlm.nih.gov/pubmed/31290355 http://dx.doi.org/10.1080/13880209.2019.1636828 |
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author | Liu, Wei Liu, Guozhi Liu, Jing |
author_facet | Liu, Wei Liu, Guozhi Liu, Jing |
author_sort | Liu, Wei |
collection | PubMed |
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 AUC(0–) (t) (717.20 ± 177.63 vs. 1166.25 ± 186.65 ng h/mL) and C (max) (272.35 ± 25.81 vs. 366.34 ± 32.57 ng/mL). The t (1/2) 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 | Online Article Text |
id | pubmed-6691885 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-66918852019-08-23 Effects of astragaloside IV on the pharmacokinetics of omeprazole in rats Liu, Wei Liu, Guozhi Liu, Jing Pharm Biol Research Article 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 AUC(0–) (t) (717.20 ± 177.63 vs. 1166.25 ± 186.65 ng h/mL) and C (max) (272.35 ± 25.81 vs. 366.34 ± 32.57 ng/mL). The t (1/2) 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. Taylor & Francis 2019-07-10 /pmc/articles/PMC6691885/ /pubmed/31290355 http://dx.doi.org/10.1080/13880209.2019.1636828 Text en © 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. http://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/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Liu, Wei Liu, Guozhi Liu, Jing Effects of astragaloside IV on the pharmacokinetics of omeprazole in rats |
title | 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_short | Effects of astragaloside IV on the pharmacokinetics of omeprazole in rats |
title_sort | effects of astragaloside iv on the pharmacokinetics of omeprazole in rats |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6691885/ https://www.ncbi.nlm.nih.gov/pubmed/31290355 http://dx.doi.org/10.1080/13880209.2019.1636828 |
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