Measurement of Hepatic CYP3A4 and 2D6 Activity Using Radioiodine-Labeled <i>O</i>-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...
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MDPI AG
2022-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/19/11458 |
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| author | Asuka Mizutani Masato Kobayashi Riku Aibe Yuka Muranaka Kodai Nishi Masanori Kitamura Chie Suzuki Ryuichi Nishii Naoto Shikano Yasuhiro Magata Yasushi Ishida Munetaka Kunishima Keiichi Kawai |
| author_facet | Asuka Mizutani Masato Kobayashi Riku Aibe Yuka Muranaka Kodai Nishi Masanori Kitamura Chie Suzuki Ryuichi Nishii Naoto Shikano Yasuhiro Magata Yasushi Ishida Munetaka Kunishima Keiichi Kawai |
| author_sort | Asuka Mizutani |
| collection | DOAJ |
| 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 <i>O</i>-desmethylvenlafaxine (<sup>123/125</sup>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 <sup>123</sup>I-ODV accumulated early in the liver and was excreted into the gallbladder, as evaluated by time activity curves. In its biological distribution, <sup>125</sup>I-ODV administered to mice accumulated early in the liver, and only the metabolite of <sup>125</sup>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, <sup>123/125</sup>I-ODV has the potential to direct, comprehensive detection and measurement of hepatic CYP3A4 and CYP2D6 activity by a simple and less invasive approach. |
| first_indexed | 2024-03-09T21:39:56Z |
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| id | doaj.art-2e3013b9f94347ffbde457974e91891d |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T21:39:56Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-2e3013b9f94347ffbde457974e91891d2023-11-23T20:33:33ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-09-0123191145810.3390/ijms231911458Measurement of Hepatic CYP3A4 and 2D6 Activity Using Radioiodine-Labeled <i>O</i>-DesmethylvenlafaxineAsuka Mizutani0Masato Kobayashi1Riku Aibe2Yuka Muranaka3Kodai Nishi4Masanori Kitamura5Chie Suzuki6Ryuichi Nishii7Naoto Shikano8Yasuhiro Magata9Yasushi Ishida10Munetaka Kunishima11Keiichi Kawai12Faculty of Health Sciences, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, 5-11-80 Kodatsuno, Kanazawa 920-0942, Ishikawa, JapanFaculty of Health Sciences, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, 5-11-80 Kodatsuno, Kanazawa 920-0942, Ishikawa, JapanDivision of Health Sciences, Graduate School of Medical Sciences, Kanazawa University, 5-11-80 Kodatsuno, Kanazawa 920-0942, Ishikawa, JapanDivision of Health Sciences, Graduate School of Medical Sciences, Kanazawa University, 5-11-80 Kodatsuno, Kanazawa 920-0942, Ishikawa, JapanDepartment of Radioisotope Medicine, Atomic Bomb Disease Institute, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Nagasaki, JapanFaculty of Pharmaceutical Sciences, Matsuyama University, 4-2 Bunkyo-cho, Matsuyama 790-8578, Ehime, JapanPreeminent Medical Photonics Education & Research Center, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi, Hamamatsu 431-3192, Shizuoka, JapanDepartment of Molecular Imaging and Theranostics, Institute for Quantum Medical Science, Quantum Life and Medical Science Directorate, National Institutes for Quantum and Radiological Science and Technology, 4-9-1 Anagawa, Inage, Chiba 263-8555, Chiba, JapanDepartment of Radiological Sciences, Ibaraki Prefectural University of Health Sciences, 4669-2 Ami, Inashiki 300-0394, Ibaraki, JapanPreeminent Medical Photonics Education & Research Center, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi, Hamamatsu 431-3192, Shizuoka, JapanDepartment of Psychiatry, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Miyazaki, JapanFaculty of Pharmaceutical Sciences, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kakuma, Kanazawa 920-1192, Ishikawa, JapanFaculty of Health Sciences, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, 5-11-80 Kodatsuno, Kanazawa 920-0942, Ishikawa, JapanDrug 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 <i>O</i>-desmethylvenlafaxine (<sup>123/125</sup>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 <sup>123</sup>I-ODV accumulated early in the liver and was excreted into the gallbladder, as evaluated by time activity curves. In its biological distribution, <sup>125</sup>I-ODV administered to mice accumulated early in the liver, and only the metabolite of <sup>125</sup>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, <sup>123/125</sup>I-ODV has the potential to direct, comprehensive detection and measurement of hepatic CYP3A4 and CYP2D6 activity by a simple and less invasive approach.https://www.mdpi.com/1422-0067/23/19/11458<i>O</i>-desmethylvenlafaxinewhole-body imagingCYP3A4CYP2D6individualized medicine |
| spellingShingle | Asuka Mizutani Masato Kobayashi Riku Aibe Yuka Muranaka Kodai Nishi Masanori Kitamura Chie Suzuki Ryuichi Nishii Naoto Shikano Yasuhiro Magata Yasushi Ishida Munetaka Kunishima Keiichi Kawai Measurement of Hepatic CYP3A4 and 2D6 Activity Using Radioiodine-Labeled <i>O</i>-Desmethylvenlafaxine International Journal of Molecular Sciences <i>O</i>-desmethylvenlafaxine whole-body imaging CYP3A4 CYP2D6 individualized medicine |
| title | Measurement of Hepatic CYP3A4 and 2D6 Activity Using Radioiodine-Labeled <i>O</i>-Desmethylvenlafaxine |
| title_full | Measurement of Hepatic CYP3A4 and 2D6 Activity Using Radioiodine-Labeled <i>O</i>-Desmethylvenlafaxine |
| title_fullStr | Measurement of Hepatic CYP3A4 and 2D6 Activity Using Radioiodine-Labeled <i>O</i>-Desmethylvenlafaxine |
| title_full_unstemmed | Measurement of Hepatic CYP3A4 and 2D6 Activity Using Radioiodine-Labeled <i>O</i>-Desmethylvenlafaxine |
| title_short | Measurement of Hepatic CYP3A4 and 2D6 Activity Using Radioiodine-Labeled <i>O</i>-Desmethylvenlafaxine |
| title_sort | measurement of hepatic cyp3a4 and 2d6 activity using radioiodine labeled i o i desmethylvenlafaxine |
| topic | <i>O</i>-desmethylvenlafaxine whole-body imaging CYP3A4 CYP2D6 individualized medicine |
| url | https://www.mdpi.com/1422-0067/23/19/11458 |
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