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
Affiliations
Kakeru Sato
Division of Health Sciences, Graduate School of Medical Sciences, Kanazawa University, 5-11-80 Kodatsuno, Kanazawa 920-0942, Japan
Asuka Mizutani
Faculty of Health Sciences, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, 5-11-80 Kodatsuno, Kanazawa 920-0942, Japan
Yuka Muranaka
Division of Health Sciences, Graduate School of Medical Sciences, Kanazawa University, 5-11-80 Kodatsuno, Kanazawa 920-0942, Japan
Jianwei Yao
Division of Health Sciences, Graduate School of Medical Sciences, Kanazawa University, 5-11-80 Kodatsuno, Kanazawa 920-0942, Japan
Masato Kobayashi
Faculty of Health Sciences, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, 5-11-80 Kodatsuno, Kanazawa 920-0942, Japan
Kana Yamazaki
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
Ryuichi Nishii
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
Kodai Nishi
Department of Radioisotope Medicine, Atomic Bomb Disease Institute, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan
Takeo Nakanishi
Faculty of Pharmacy, Takasaki University of Health and Welfare, 60 Nakaorui-machi, Takasaki 370-0033, Japan
Ikumi Tamai
Faculty of Pharmaceutical Sciences, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kakuma, Kanazawa 920-1192, Japan
Keiichi Kawai
Faculty of Health Sciences, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, 5-11-80 Kodatsuno, Kanazawa 920-0942, Japan
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.
