Biological Distribution after Oral Administration of Radioiodine-Labeled Acetaminophen to Estimate Gastrointestinal Absorption Function via OATPs, OATs, and/or MRPs
We evaluated the whole-body distribution of orally-administered radioiodine-125 labeled acetaminophen (<sup>125</sup>I-AP) to estimate gastrointestinal absorption of anionic drugs. <sup>125</sup>I-AP was added to human embryonic kidney (HEK)293 and Flp293 cells expressing hum...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-02-01
|
| Series: | Pharmaceutics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4923/15/2/497 |
| _version_ | 1797618776885166080 |
|---|---|
| author | Kakeru Sato Asuka Mizutani Yuka Muranaka Jianwei Yao Masato Kobayashi Kana Yamazaki Ryuichi Nishii Kodai Nishi Takeo Nakanishi Ikumi Tamai Keiichi Kawai |
| author_facet | Kakeru Sato Asuka Mizutani Yuka Muranaka Jianwei Yao Masato Kobayashi Kana Yamazaki Ryuichi Nishii Kodai Nishi Takeo Nakanishi Ikumi Tamai Keiichi Kawai |
| author_sort | Kakeru Sato |
| collection | DOAJ |
| description | We evaluated the whole-body distribution of orally-administered radioiodine-125 labeled acetaminophen (<sup>125</sup>I-AP) to estimate gastrointestinal absorption of anionic drugs. <sup>125</sup>I-AP was added to human embryonic kidney (HEK)293 and Flp293 cells expressing human organic anion transporting polypeptide (OATP)1B1/3, OATP2B1, organic anion transporter (OAT)1/2/3, or carnitine/organic cation transporter (OCTN)2, with and without bromosulfalein (OATP and multidrug resistance-associated protein (MRP) inhibitor) and probenecid (OAT and MRP inhibitor). The biological distribution in mice was determined by oral administration of <sup>125</sup>I-AP with and without bromosulfalein and by intravenous administration of <sup>125</sup>I-AP. The uptake of <sup>125</sup>I-AP was significantly higher in HEK293/OATP1B1, OATP1B3, OATP2B1, OAT1, and OAT2 cells than that in mock cells. Bromosulfalein and probenecid inhibited OATP- and OAT-mediated uptake, respectively. Moreover, <sup>125</sup>I-AP was easily excreted in the urine when administered intravenously. The accumulation of <sup>125</sup>I-AP was significantly lower in the blood and urinary bladder of mice receiving oral administration of both <sup>125</sup>I-AP and bromosulfalein than those receiving only <sup>125</sup>I-AP, but significantly higher in the small intestine due to inhibition of OATPs and/or MRPs. This study indicates that whole-body distribution after oral <sup>125</sup>I-AP administration can be used to estimate gastrointestinal absorption in the small intestine via OATPs, OATs, and/or MRPs by measuring radioactivity in the urinary bladder. |
| first_indexed | 2024-03-11T08:17:23Z |
| format | Article |
| id | doaj.art-da3085bf15624b42aa1e36fd55e208bf |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-11T08:17:23Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-da3085bf15624b42aa1e36fd55e208bf2023-11-16T22:40:43ZengMDPI AGPharmaceutics1999-49232023-02-0115249710.3390/pharmaceutics15020497Biological Distribution after Oral Administration of Radioiodine-Labeled Acetaminophen to Estimate Gastrointestinal Absorption Function via OATPs, OATs, and/or MRPsKakeru Sato0Asuka Mizutani1Yuka Muranaka2Jianwei Yao3Masato Kobayashi4Kana Yamazaki5Ryuichi Nishii6Kodai Nishi7Takeo Nakanishi8Ikumi Tamai9Keiichi Kawai10Division of Health Sciences, Graduate School of Medical Sciences, Kanazawa University, 5-11-80 Kodatsuno, Kanazawa 920-0942, JapanFaculty of Health Sciences, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, 5-11-80 Kodatsuno, Kanazawa 920-0942, JapanDivision of Health Sciences, Graduate School of Medical Sciences, Kanazawa University, 5-11-80 Kodatsuno, Kanazawa 920-0942, JapanDivision of Health Sciences, Graduate School of Medical Sciences, Kanazawa University, 5-11-80 Kodatsuno, Kanazawa 920-0942, JapanFaculty of Health Sciences, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, 5-11-80 Kodatsuno, Kanazawa 920-0942, JapanDepartment of Molecular Imaging and Theranostics, Institute for Quantum Medical Science, Quantum Life and Medical Science Directorate, National Institutes for Quantum Science and Technology, 4-9-1 Anagawa, Inage 263-8555, JapanDepartment of Molecular Imaging and Theranostics, Institute for Quantum Medical Science, Quantum Life and Medical Science Directorate, National Institutes for Quantum Science and Technology, 4-9-1 Anagawa, Inage 263-8555, JapanDepartment of Radioisotope Medicine, Atomic Bomb Disease Institute, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, JapanFaculty of Pharmacy, Takasaki University of Health and Welfare, 60 Nakaorui-machi, Takasaki 370-0033, JapanFaculty of Pharmaceutical Sciences, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kakuma, Kanazawa 920-1192, JapanFaculty of Health Sciences, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, 5-11-80 Kodatsuno, Kanazawa 920-0942, JapanWe evaluated the whole-body distribution of orally-administered radioiodine-125 labeled acetaminophen (<sup>125</sup>I-AP) to estimate gastrointestinal absorption of anionic drugs. <sup>125</sup>I-AP was added to human embryonic kidney (HEK)293 and Flp293 cells expressing human organic anion transporting polypeptide (OATP)1B1/3, OATP2B1, organic anion transporter (OAT)1/2/3, or carnitine/organic cation transporter (OCTN)2, with and without bromosulfalein (OATP and multidrug resistance-associated protein (MRP) inhibitor) and probenecid (OAT and MRP inhibitor). The biological distribution in mice was determined by oral administration of <sup>125</sup>I-AP with and without bromosulfalein and by intravenous administration of <sup>125</sup>I-AP. The uptake of <sup>125</sup>I-AP was significantly higher in HEK293/OATP1B1, OATP1B3, OATP2B1, OAT1, and OAT2 cells than that in mock cells. Bromosulfalein and probenecid inhibited OATP- and OAT-mediated uptake, respectively. Moreover, <sup>125</sup>I-AP was easily excreted in the urine when administered intravenously. The accumulation of <sup>125</sup>I-AP was significantly lower in the blood and urinary bladder of mice receiving oral administration of both <sup>125</sup>I-AP and bromosulfalein than those receiving only <sup>125</sup>I-AP, but significantly higher in the small intestine due to inhibition of OATPs and/or MRPs. This study indicates that whole-body distribution after oral <sup>125</sup>I-AP administration can be used to estimate gastrointestinal absorption in the small intestine via OATPs, OATs, and/or MRPs by measuring radioactivity in the urinary bladder.https://www.mdpi.com/1999-4923/15/2/497gastrointestinal absorptionanion drugs and medicines<sup>125</sup>I-acetaminophenoral administrationdrug transporters |
| spellingShingle | Kakeru Sato Asuka Mizutani Yuka Muranaka Jianwei Yao Masato Kobayashi Kana Yamazaki Ryuichi Nishii Kodai Nishi Takeo Nakanishi Ikumi Tamai Keiichi Kawai Biological Distribution after Oral Administration of Radioiodine-Labeled Acetaminophen to Estimate Gastrointestinal Absorption Function via OATPs, OATs, and/or MRPs Pharmaceutics gastrointestinal absorption anion drugs and medicines <sup>125</sup>I-acetaminophen oral administration drug transporters |
| title | Biological Distribution after Oral Administration of Radioiodine-Labeled Acetaminophen to Estimate Gastrointestinal Absorption Function via OATPs, OATs, and/or MRPs |
| title_full | Biological Distribution after Oral Administration of Radioiodine-Labeled Acetaminophen to Estimate Gastrointestinal Absorption Function via OATPs, OATs, and/or MRPs |
| title_fullStr | Biological Distribution after Oral Administration of Radioiodine-Labeled Acetaminophen to Estimate Gastrointestinal Absorption Function via OATPs, OATs, and/or MRPs |
| title_full_unstemmed | Biological Distribution after Oral Administration of Radioiodine-Labeled Acetaminophen to Estimate Gastrointestinal Absorption Function via OATPs, OATs, and/or MRPs |
| title_short | Biological Distribution after Oral Administration of Radioiodine-Labeled Acetaminophen to Estimate Gastrointestinal Absorption Function via OATPs, OATs, and/or MRPs |
| title_sort | biological distribution after oral administration of radioiodine labeled acetaminophen to estimate gastrointestinal absorption function via oatps oats and or mrps |
| topic | gastrointestinal absorption anion drugs and medicines <sup>125</sup>I-acetaminophen oral administration drug transporters |
| url | https://www.mdpi.com/1999-4923/15/2/497 |
| work_keys_str_mv | AT kakerusato biologicaldistributionafteroraladministrationofradioiodinelabeledacetaminophentoestimategastrointestinalabsorptionfunctionviaoatpsoatsandormrps AT asukamizutani biologicaldistributionafteroraladministrationofradioiodinelabeledacetaminophentoestimategastrointestinalabsorptionfunctionviaoatpsoatsandormrps AT yukamuranaka biologicaldistributionafteroraladministrationofradioiodinelabeledacetaminophentoestimategastrointestinalabsorptionfunctionviaoatpsoatsandormrps AT jianweiyao biologicaldistributionafteroraladministrationofradioiodinelabeledacetaminophentoestimategastrointestinalabsorptionfunctionviaoatpsoatsandormrps AT masatokobayashi biologicaldistributionafteroraladministrationofradioiodinelabeledacetaminophentoestimategastrointestinalabsorptionfunctionviaoatpsoatsandormrps AT kanayamazaki biologicaldistributionafteroraladministrationofradioiodinelabeledacetaminophentoestimategastrointestinalabsorptionfunctionviaoatpsoatsandormrps AT ryuichinishii biologicaldistributionafteroraladministrationofradioiodinelabeledacetaminophentoestimategastrointestinalabsorptionfunctionviaoatpsoatsandormrps AT kodainishi biologicaldistributionafteroraladministrationofradioiodinelabeledacetaminophentoestimategastrointestinalabsorptionfunctionviaoatpsoatsandormrps AT takeonakanishi biologicaldistributionafteroraladministrationofradioiodinelabeledacetaminophentoestimategastrointestinalabsorptionfunctionviaoatpsoatsandormrps AT ikumitamai biologicaldistributionafteroraladministrationofradioiodinelabeledacetaminophentoestimategastrointestinalabsorptionfunctionviaoatpsoatsandormrps AT keiichikawai biologicaldistributionafteroraladministrationofradioiodinelabeledacetaminophentoestimategastrointestinalabsorptionfunctionviaoatpsoatsandormrps |