Pharmacokinetic interactions of niclosamide in rats: Involvement of organic anion transporters 1 and 3 and organic cation transporter 2.

Autor: Kang MJ; College of Pharmacy, Woosuk University, Wanju, 55338, Republic of Korea., Kim MJ; Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju, 28116, Republic of Korea., Kim A; College of Pharmacy, Woosuk University, Wanju, 55338, Republic of Korea., Koo TS; Graduate School of New Drug Discovery and Development, Chungnam National University, Daejeon, 34134, Republic of Korea., Lee KR; Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju, 28116, Republic of Korea; Department of Bioscience, University of Science and Technology, Daejeon, 34113, Republic of Korea. Electronic address: kyeongrlee@kribb.re.kr., Chae YJ; College of Pharmacy, Woosuk University, Wanju, 55338, Republic of Korea; Research Institute of Pharmaceutical Sciences, Woosuk University, Wanju, 55338, Republic of Korea. Electronic address: yjchae@woosuk.ac.kr.
Jazyk: angličtina
Zdroj: Chemico-biological interactions [Chem Biol Interact] 2024 Feb 25; Vol. 390, pp. 110886. Date of Electronic Publication: 2024 Jan 25.
DOI: 10.1016/j.cbi.2024.110886
Abstrakt: Niclosamide is an anthelmintic drug with a long history of use and is generally safe and well tolerated in humans. As the conventional dose of niclosamide results in a low but certain level in systemic circulation, drug interactions with concomitant drugs should be considered. We aimed to investigate the interaction between niclosamide and drug transporters, as such information is currently limited. Niclosamide inhibited the transport activity of OATP1B1, OATP1B3, OAT1, OAT3, and OCT2 in vitro. Among them, the inhibitory effects on OAT1, OAT3, and OCT2 were strong, with IC 50 values of less than 1 μM. When 3 mg/kg of niclosamide was co-administered to rats, systemic exposure to furosemide (a substrate of OAT1/3) and metformin (a substrate of OCT2) increased, and the renal clearance (CL r ) of the drugs significantly decreased. These results suggest that niclosamide inhibits renal transporters, OAT1/3 and OCT2, not only in vitro but also in vivo, resulting in increased systemic exposure to the substrates of the transporters by strongly blocking the urinary elimination pathway in rats. The findings of this study will support a meticulous understanding of the transporter-mediated drug interactions of niclosamide and consequently aid in effective and safe use of niclosamide.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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