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

Automated summary

This study evaluated the distribution of radioiodine-125 labeled acetaminophen (I-125-AP) in the body after oral administration, aiming to estimate the absorption of anionic drugs in the gastrointestinal tract. The results showed that the uptake of I-125-AP was significantly higher in cells expressing certain transporters and inhibited by specific inhibitors. Furthermore, the distribution of I-125-AP in mice indicated that the small intestine plays a crucial role in the absorption process mediated by OATPs, OATs, and/or MRPs.