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Effect of finasteride particle size reduction on its pharmacokinetic, tissue distribution and cellular permeation
Finasteride (FSD), a specific competitive inhibitor of the steroid type-II 5α-reductase enzyme, is used in treatment of benign prostate hyperplasia (BPH) and male pattern baldness. The drug is of limited solubility that affect its dissolution and bioavailability. The aim was to study the effect of F...
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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/PMC6058569/ https://www.ncbi.nlm.nih.gov/pubmed/29451038 http://dx.doi.org/10.1080/10717544.2018.1440446 |
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author | Ahmed, Tarek A. Al-Abd, Ahmed M. |
author_facet | Ahmed, Tarek A. Al-Abd, Ahmed M. |
author_sort | Ahmed, Tarek A. |
collection | PubMed |
description | Finasteride (FSD), a specific competitive inhibitor of the steroid type-II 5α-reductase enzyme, is used in treatment of benign prostate hyperplasia (BPH) and male pattern baldness. The drug is of limited solubility that affect its dissolution and bioavailability. The aim was to study the effect of FSD particle size reduction on the pharmacokinetic, tissue distribution and cellular permeation. An optimized drug micro- and nano-particles were developed, characterized, administered to group of rats, and systemic pharmacokinetic and tissue distribution within target and not-target organs were determined using near-infrared (NIR) spectroscopy technique. Moreover, the cellular permeation of the prepared formulations through normal prostate epithelial cells was assessed and compared to pure FSD. The developed micro- and nano-particles were of 930 and 645 nm, respectively. Plasma maximum drug levels (C(max)) and overall exposure (AUC) of both formulations were not significantly higher than unformulated drug. However, micronized FSD achieved significant higher concentration within the target tissue (prostate) within the current study compared to pure drug and nano-sized formulation as well. Yet, this is explained by the higher sequestration ability of spleen tissue to the nano-sized formula compared to micro-sized FSD. At the cellular level, permeation of nano-sized FSD through prostate epithelial cells was superior to the unformulated FSD as well as the micro-sized drug formulation. FSD particle size reduction significantly influences its cellular permeation and to a lesser extend affect its systemic pharmacokinetics and tissue distribution after oral administration. |
format | Online Article Text |
id | pubmed-6058569 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-60585692018-08-17 Effect of finasteride particle size reduction on its pharmacokinetic, tissue distribution and cellular permeation Ahmed, Tarek A. Al-Abd, Ahmed M. Drug Deliv Research Article Finasteride (FSD), a specific competitive inhibitor of the steroid type-II 5α-reductase enzyme, is used in treatment of benign prostate hyperplasia (BPH) and male pattern baldness. The drug is of limited solubility that affect its dissolution and bioavailability. The aim was to study the effect of FSD particle size reduction on the pharmacokinetic, tissue distribution and cellular permeation. An optimized drug micro- and nano-particles were developed, characterized, administered to group of rats, and systemic pharmacokinetic and tissue distribution within target and not-target organs were determined using near-infrared (NIR) spectroscopy technique. Moreover, the cellular permeation of the prepared formulations through normal prostate epithelial cells was assessed and compared to pure FSD. The developed micro- and nano-particles were of 930 and 645 nm, respectively. Plasma maximum drug levels (C(max)) and overall exposure (AUC) of both formulations were not significantly higher than unformulated drug. However, micronized FSD achieved significant higher concentration within the target tissue (prostate) within the current study compared to pure drug and nano-sized formulation as well. Yet, this is explained by the higher sequestration ability of spleen tissue to the nano-sized formula compared to micro-sized FSD. At the cellular level, permeation of nano-sized FSD through prostate epithelial cells was superior to the unformulated FSD as well as the micro-sized drug formulation. FSD particle size reduction significantly influences its cellular permeation and to a lesser extend affect its systemic pharmacokinetics and tissue distribution after oral administration. Taylor & Francis 2018-02-16 /pmc/articles/PMC6058569/ /pubmed/29451038 http://dx.doi.org/10.1080/10717544.2018.1440446 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 Ahmed, Tarek A. Al-Abd, Ahmed M. Effect of finasteride particle size reduction on its pharmacokinetic, tissue distribution and cellular permeation |
title | Effect of finasteride particle size reduction on its pharmacokinetic, tissue distribution and cellular permeation |
title_full | Effect of finasteride particle size reduction on its pharmacokinetic, tissue distribution and cellular permeation |
title_fullStr | Effect of finasteride particle size reduction on its pharmacokinetic, tissue distribution and cellular permeation |
title_full_unstemmed | Effect of finasteride particle size reduction on its pharmacokinetic, tissue distribution and cellular permeation |
title_short | Effect of finasteride particle size reduction on its pharmacokinetic, tissue distribution and cellular permeation |
title_sort | effect of finasteride particle size reduction on its pharmacokinetic, tissue distribution and cellular permeation |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6058569/ https://www.ncbi.nlm.nih.gov/pubmed/29451038 http://dx.doi.org/10.1080/10717544.2018.1440446 |
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