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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
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.
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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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