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Effects of psoralen on the pharmacokinetics of anastrozole in rats
Context: Psoralen and anastrozole are always used together for breast cancer patients in Chinese clinics. Objective: This study investigates the effects of psoralen on the pharmacokinetics of anastrozole in rats and its potential mechanism. Materials and methods: The pharmacokinetics of orally admin...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6201813/ https://www.ncbi.nlm.nih.gov/pubmed/30345900 http://dx.doi.org/10.1080/13880209.2018.1501584 |
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author | Zhang, Yuzhu Wu, Jingjing Zhou, Yue Yin, Yulian Chen, Hongfeng |
author_facet | Zhang, Yuzhu Wu, Jingjing Zhou, Yue Yin, Yulian Chen, Hongfeng |
author_sort | Zhang, Yuzhu |
collection | PubMed |
description | Context: Psoralen and anastrozole are always used together for breast cancer patients in Chinese clinics. Objective: This study investigates the effects of psoralen on the pharmacokinetics of anastrozole in rats and its potential mechanism. Materials and methods: The pharmacokinetics of orally administered anastrozole (0.5 mg/kg) with (test group) or without (Control group) psoralen pretreatment (20 mg/kg/day for 10 days) in male Sprague-Dawley rats (six rats in each group) were investigated. The plasma concentration of anastrozole was determined using a sensitive and reliable LC-MS/MS method. Additionally, the effects of psoralen on the intestine transport and metabolic stability of anastrozole (1 μM) were investigated using a Caco-2 cell transwell model and rat liver microsome incubation systems. Results: The results indicated that psoralen could significantly increase the C(max) (from 56.74 ± 3.17 ng/mL to 83.26 ± 6.87 ng/mL), and t(1/2) (from 10.80 ± 1.05 to 14.29 ± 1.38 h) of anastrozole (p < 0.05). Psoralen could also significantly decrease the efflux ratio of anastrozole from 1.88 to 1.32 (p < 0.05). Additionally, the intrinsic clearance rates of anastrozole decreased significantly (from 62.83 to 43.97 μL/min/mg protein) (p < 0.05) with psoralen pretreatment in rat liver microsome incubation systems. Discussion and conclusions: This study indicates that when the rats were pretreated with psoralen, the system exposure of anastrozole would be increased significantly. The results showed that the herb-drug interaction between psoralen and anastrozole might occur when they were co-administered, and future studies in humans also need to investigate its herb-drug interaction potential. |
format | Online Article Text |
id | pubmed-6201813 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-62018132018-10-26 Effects of psoralen on the pharmacokinetics of anastrozole in rats Zhang, Yuzhu Wu, Jingjing Zhou, Yue Yin, Yulian Chen, Hongfeng Pharm Biol Research Article Context: Psoralen and anastrozole are always used together for breast cancer patients in Chinese clinics. Objective: This study investigates the effects of psoralen on the pharmacokinetics of anastrozole in rats and its potential mechanism. Materials and methods: The pharmacokinetics of orally administered anastrozole (0.5 mg/kg) with (test group) or without (Control group) psoralen pretreatment (20 mg/kg/day for 10 days) in male Sprague-Dawley rats (six rats in each group) were investigated. The plasma concentration of anastrozole was determined using a sensitive and reliable LC-MS/MS method. Additionally, the effects of psoralen on the intestine transport and metabolic stability of anastrozole (1 μM) were investigated using a Caco-2 cell transwell model and rat liver microsome incubation systems. Results: The results indicated that psoralen could significantly increase the C(max) (from 56.74 ± 3.17 ng/mL to 83.26 ± 6.87 ng/mL), and t(1/2) (from 10.80 ± 1.05 to 14.29 ± 1.38 h) of anastrozole (p < 0.05). Psoralen could also significantly decrease the efflux ratio of anastrozole from 1.88 to 1.32 (p < 0.05). Additionally, the intrinsic clearance rates of anastrozole decreased significantly (from 62.83 to 43.97 μL/min/mg protein) (p < 0.05) with psoralen pretreatment in rat liver microsome incubation systems. Discussion and conclusions: This study indicates that when the rats were pretreated with psoralen, the system exposure of anastrozole would be increased significantly. The results showed that the herb-drug interaction between psoralen and anastrozole might occur when they were co-administered, and future studies in humans also need to investigate its herb-drug interaction potential. Taylor & Francis 2018-10-21 /pmc/articles/PMC6201813/ /pubmed/30345900 http://dx.doi.org/10.1080/13880209.2018.1501584 Text en © 2018 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 Zhang, Yuzhu Wu, Jingjing Zhou, Yue Yin, Yulian Chen, Hongfeng Effects of psoralen on the pharmacokinetics of anastrozole in rats |
title | Effects of psoralen on the pharmacokinetics of anastrozole in rats |
title_full | Effects of psoralen on the pharmacokinetics of anastrozole in rats |
title_fullStr | Effects of psoralen on the pharmacokinetics of anastrozole in rats |
title_full_unstemmed | Effects of psoralen on the pharmacokinetics of anastrozole in rats |
title_short | Effects of psoralen on the pharmacokinetics of anastrozole in rats |
title_sort | effects of psoralen on the pharmacokinetics of anastrozole in rats |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6201813/ https://www.ncbi.nlm.nih.gov/pubmed/30345900 http://dx.doi.org/10.1080/13880209.2018.1501584 |
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