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Measurement of Hepatic CYP3A4 and 2D6 Activity Using Radioiodine-Labeled O-Desmethylvenlafaxine
Drug metabolizing enzyme activity is affected by various factors such as drug–drug interactions, and a method to quantify drug metabolizing enzyme activity in real time is needed. In this study, we developed a novel radiopharmaceutical for quantitative imaging to estimate hepatic CYP3A4 and CYP2D6 a...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9569593/ https://www.ncbi.nlm.nih.gov/pubmed/36232758 http://dx.doi.org/10.3390/ijms231911458 |
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author | Mizutani, Asuka Kobayashi, Masato Aibe, Riku Muranaka, Yuka Nishi, Kodai Kitamura, Masanori Suzuki, Chie Nishii, Ryuichi Shikano, Naoto Magata, Yasuhiro Ishida, Yasushi Kunishima, Munetaka Kawai, Keiichi |
author_facet | Mizutani, Asuka Kobayashi, Masato Aibe, Riku Muranaka, Yuka Nishi, Kodai Kitamura, Masanori Suzuki, Chie Nishii, Ryuichi Shikano, Naoto Magata, Yasuhiro Ishida, Yasushi Kunishima, Munetaka Kawai, Keiichi |
author_sort | Mizutani, Asuka |
collection | PubMed |
description | Drug metabolizing enzyme activity is affected by various factors such as drug–drug interactions, and a method to quantify drug metabolizing enzyme activity in real time is needed. In this study, we developed a novel radiopharmaceutical for quantitative imaging to estimate hepatic CYP3A4 and CYP2D6 activity. Iodine-123- and 125-labeled O-desmethylvenlafaxine ((123/125)I-ODV) was obtained with high labeling and purity, and its metabolism was found to strongly involve CYP3A4 and CYP2D6. SPECT imaging in normal mice showed that the administered (123)I-ODV accumulated early in the liver and was excreted into the gallbladder, as evaluated by time activity curves. In its biological distribution, (125)I-ODV administered to mice accumulated early in the liver, and only the metabolite of (125)I-ODV was quickly excreted into the bile. In CYP3A4- and CYP2D6-inhibited model mice, the accumulation in bile decreased more than in normal mice, indicating inhibition of metabolite production. These results indicated that imaging and quantifying the accumulation of radioactive metabolites in excretory organs will aid in determining the dosages of various drugs metabolized by CYP3A4 and CYP2D6 for individualized medicine. Thus, (123/125)I-ODV has the potential to direct, comprehensive detection and measurement of hepatic CYP3A4 and CYP2D6 activity by a simple and less invasive approach. |
format | Online Article Text |
id | pubmed-9569593 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-95695932022-10-17 Measurement of Hepatic CYP3A4 and 2D6 Activity Using Radioiodine-Labeled O-Desmethylvenlafaxine Mizutani, Asuka Kobayashi, Masato Aibe, Riku Muranaka, Yuka Nishi, Kodai Kitamura, Masanori Suzuki, Chie Nishii, Ryuichi Shikano, Naoto Magata, Yasuhiro Ishida, Yasushi Kunishima, Munetaka Kawai, Keiichi Int J Mol Sci Article Drug metabolizing enzyme activity is affected by various factors such as drug–drug interactions, and a method to quantify drug metabolizing enzyme activity in real time is needed. In this study, we developed a novel radiopharmaceutical for quantitative imaging to estimate hepatic CYP3A4 and CYP2D6 activity. Iodine-123- and 125-labeled O-desmethylvenlafaxine ((123/125)I-ODV) was obtained with high labeling and purity, and its metabolism was found to strongly involve CYP3A4 and CYP2D6. SPECT imaging in normal mice showed that the administered (123)I-ODV accumulated early in the liver and was excreted into the gallbladder, as evaluated by time activity curves. In its biological distribution, (125)I-ODV administered to mice accumulated early in the liver, and only the metabolite of (125)I-ODV was quickly excreted into the bile. In CYP3A4- and CYP2D6-inhibited model mice, the accumulation in bile decreased more than in normal mice, indicating inhibition of metabolite production. These results indicated that imaging and quantifying the accumulation of radioactive metabolites in excretory organs will aid in determining the dosages of various drugs metabolized by CYP3A4 and CYP2D6 for individualized medicine. Thus, (123/125)I-ODV has the potential to direct, comprehensive detection and measurement of hepatic CYP3A4 and CYP2D6 activity by a simple and less invasive approach. MDPI 2022-09-28 /pmc/articles/PMC9569593/ /pubmed/36232758 http://dx.doi.org/10.3390/ijms231911458 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Mizutani, Asuka Kobayashi, Masato Aibe, Riku Muranaka, Yuka Nishi, Kodai Kitamura, Masanori Suzuki, Chie Nishii, Ryuichi Shikano, Naoto Magata, Yasuhiro Ishida, Yasushi Kunishima, Munetaka Kawai, Keiichi Measurement of Hepatic CYP3A4 and 2D6 Activity Using Radioiodine-Labeled O-Desmethylvenlafaxine |
title | Measurement of Hepatic CYP3A4 and 2D6 Activity Using Radioiodine-Labeled O-Desmethylvenlafaxine |
title_full | Measurement of Hepatic CYP3A4 and 2D6 Activity Using Radioiodine-Labeled O-Desmethylvenlafaxine |
title_fullStr | Measurement of Hepatic CYP3A4 and 2D6 Activity Using Radioiodine-Labeled O-Desmethylvenlafaxine |
title_full_unstemmed | Measurement of Hepatic CYP3A4 and 2D6 Activity Using Radioiodine-Labeled O-Desmethylvenlafaxine |
title_short | Measurement of Hepatic CYP3A4 and 2D6 Activity Using Radioiodine-Labeled O-Desmethylvenlafaxine |
title_sort | measurement of hepatic cyp3a4 and 2d6 activity using radioiodine-labeled o-desmethylvenlafaxine |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9569593/ https://www.ncbi.nlm.nih.gov/pubmed/36232758 http://dx.doi.org/10.3390/ijms231911458 |
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