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Investigation of the Factors Responsible for the Poor Oral Bioavailability of Acacetin in Rats: Physicochemical and Biopharmaceutical Aspects
Acacetin, an important ingredient of acacia honey and a component of several medicinal plants, exhibits therapeutic effects such as antioxidative, anticancer, anti-inflammatory, and anti-plasmodial activities. However, to date, studies reporting a systematic investigation of the in vivo fate of oral...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7911516/ https://www.ncbi.nlm.nih.gov/pubmed/33525442 http://dx.doi.org/10.3390/pharmaceutics13020175 |
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author | Han, Dong-Gyun Cha, Eunju Joo, Jeongmin Hwang, Ji Sun Kim, Sanghyun Park, Taeuk Jeong, Yoo-Seong Maeng, Han-Joo Kim, Sang-Bum Yoon, In-Soo |
author_facet | Han, Dong-Gyun Cha, Eunju Joo, Jeongmin Hwang, Ji Sun Kim, Sanghyun Park, Taeuk Jeong, Yoo-Seong Maeng, Han-Joo Kim, Sang-Bum Yoon, In-Soo |
author_sort | Han, Dong-Gyun |
collection | PubMed |
description | Acacetin, an important ingredient of acacia honey and a component of several medicinal plants, exhibits therapeutic effects such as antioxidative, anticancer, anti-inflammatory, and anti-plasmodial activities. However, to date, studies reporting a systematic investigation of the in vivo fate of orally administered acacetin are limited. Moreover, the in vitro physicochemical and biopharmaceutical properties of acacetin in the gastrointestinal (GI) tract and their pharmacokinetic impacts remain unclear. Therefore, in this study, we aimed to systematically investigate the oral absorption and disposition of acacetin using relevant rat models. Acacetin exhibited poor solubility (≤119 ng/mL) and relatively low stability (27.5–62.0% remaining after 24 h) in pH 7 phosphate buffer and simulated GI fluids. A major portion (97.1%) of the initially injected acacetin dose remained unabsorbed in the jejunal segments, and the oral bioavailability of acacetin was very low at 2.34%. The systemic metabolism of acacetin occurred ubiquitously in various tissues (particularly in the liver, where it occurred most extensively), resulting in very high total plasma clearance of 199 ± 36 mL/min/kg. Collectively, the poor oral bioavailability of acacetin could be attributed mainly to its poor solubility and low GI luminal stability. |
format | Online Article Text |
id | pubmed-7911516 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-79115162021-02-28 Investigation of the Factors Responsible for the Poor Oral Bioavailability of Acacetin in Rats: Physicochemical and Biopharmaceutical Aspects Han, Dong-Gyun Cha, Eunju Joo, Jeongmin Hwang, Ji Sun Kim, Sanghyun Park, Taeuk Jeong, Yoo-Seong Maeng, Han-Joo Kim, Sang-Bum Yoon, In-Soo Pharmaceutics Article Acacetin, an important ingredient of acacia honey and a component of several medicinal plants, exhibits therapeutic effects such as antioxidative, anticancer, anti-inflammatory, and anti-plasmodial activities. However, to date, studies reporting a systematic investigation of the in vivo fate of orally administered acacetin are limited. Moreover, the in vitro physicochemical and biopharmaceutical properties of acacetin in the gastrointestinal (GI) tract and their pharmacokinetic impacts remain unclear. Therefore, in this study, we aimed to systematically investigate the oral absorption and disposition of acacetin using relevant rat models. Acacetin exhibited poor solubility (≤119 ng/mL) and relatively low stability (27.5–62.0% remaining after 24 h) in pH 7 phosphate buffer and simulated GI fluids. A major portion (97.1%) of the initially injected acacetin dose remained unabsorbed in the jejunal segments, and the oral bioavailability of acacetin was very low at 2.34%. The systemic metabolism of acacetin occurred ubiquitously in various tissues (particularly in the liver, where it occurred most extensively), resulting in very high total plasma clearance of 199 ± 36 mL/min/kg. Collectively, the poor oral bioavailability of acacetin could be attributed mainly to its poor solubility and low GI luminal stability. MDPI 2021-01-28 /pmc/articles/PMC7911516/ /pubmed/33525442 http://dx.doi.org/10.3390/pharmaceutics13020175 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Han, Dong-Gyun Cha, Eunju Joo, Jeongmin Hwang, Ji Sun Kim, Sanghyun Park, Taeuk Jeong, Yoo-Seong Maeng, Han-Joo Kim, Sang-Bum Yoon, In-Soo Investigation of the Factors Responsible for the Poor Oral Bioavailability of Acacetin in Rats: Physicochemical and Biopharmaceutical Aspects |
title | Investigation of the Factors Responsible for the Poor Oral Bioavailability of Acacetin in Rats: Physicochemical and Biopharmaceutical Aspects |
title_full | Investigation of the Factors Responsible for the Poor Oral Bioavailability of Acacetin in Rats: Physicochemical and Biopharmaceutical Aspects |
title_fullStr | Investigation of the Factors Responsible for the Poor Oral Bioavailability of Acacetin in Rats: Physicochemical and Biopharmaceutical Aspects |
title_full_unstemmed | Investigation of the Factors Responsible for the Poor Oral Bioavailability of Acacetin in Rats: Physicochemical and Biopharmaceutical Aspects |
title_short | Investigation of the Factors Responsible for the Poor Oral Bioavailability of Acacetin in Rats: Physicochemical and Biopharmaceutical Aspects |
title_sort | investigation of the factors responsible for the poor oral bioavailability of acacetin in rats: physicochemical and biopharmaceutical aspects |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7911516/ https://www.ncbi.nlm.nih.gov/pubmed/33525442 http://dx.doi.org/10.3390/pharmaceutics13020175 |
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