Biological Distribution after Oral Administration of Radioiodine-Labeled Acetaminophen to Estimate Gastrointestinal Absorption Function via OATPs, OATs, and/or MRPs

Kakeru Sato; Asuka Mizutani; Yuka Muranaka; Jianwei Yao; Masato Kobayashi; Kana Yamazaki; Ryuichi Nishii; Kodai Nishi; Takeo Nakanishi; Ikumi Tamai; Keiichi Kawai

doi:10.3390/pharmaceutics15020497

Biological Distribution after Oral Administration of Radioiodine-Labeled Acetaminophen to Estimate Gastrointestinal Absorption Function via OATPs, OATs, and/or MRPs

Pharmaceutics. 2023 Feb 2;15(2):497. doi: 10.3390/pharmaceutics15020497.

Authors

Affiliations

¹ Division of Health Sciences, Graduate School of Medical Sciences, Kanazawa University, 5-11-80 Kodatsuno, Kanazawa 920-0942, Japan.
² Faculty of Health Sciences, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, 5-11-80 Kodatsuno, Kanazawa 920-0942, Japan.
³ Department 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, Japan.
⁴ Department of Radioisotope Medicine, Atomic Bomb Disease Institute, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.
⁵ Faculty of Pharmacy, Takasaki University of Health and Welfare, 60 Nakaorui-machi, Takasaki 370-0033, Japan.
⁶ Faculty of Pharmaceutical Sciences, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kakuma, Kanazawa 920-1192, Japan.
⁷ Biomedical Imaging Research Center, University of Fukui, 23-3 Matsuokashimoaizuki, Eiheiji 910-1193, Japan.

Abstract

We evaluated the whole-body distribution of orally-administered radioiodine-125 labeled acetaminophen (¹²⁵I-AP) to estimate gastrointestinal absorption of anionic drugs. ¹²⁵I-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 ¹²⁵I-AP with and without bromosulfalein and by intravenous administration of ¹²⁵I-AP. The uptake of ¹²⁵I-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, ¹²⁵I-AP was easily excreted in the urine when administered intravenously. The accumulation of ¹²⁵I-AP was significantly lower in the blood and urinary bladder of mice receiving oral administration of both ¹²⁵I-AP and bromosulfalein than those receiving only ¹²⁵I-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 ¹²⁵I-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.

Keywords: 125I-acetaminophen; anion drugs and medicines; drug transporters; gastrointestinal absorption; oral administration.

Abstract

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