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Research ArticleABSORPTION, DISTRIBUTION, METABOLISM, AND EXCRETION

Interactions of Human Organic Anion Transporters and Human Organic Cation Transporters with Nonsteroidal Anti-Inflammatory Drugs

Suparat Khamdang, Michio Takeda, Rie Noshiro, Shinichi Narikawa, Atsushi Enomoto, Naohiko Anzai, Pawinee Piyachaturawat and Hitoshi Endou
Journal of Pharmacology and Experimental Therapeutics November 2002, 303 (2) 534-539; DOI: https://doi.org/10.1124/jpet.102.037580
Suparat Khamdang
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Michio Takeda
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Rie Noshiro
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Shinichi Narikawa
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Atsushi Enomoto
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Naohiko Anzai
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Pawinee Piyachaturawat
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Hitoshi Endou
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Abstract

The purpose of this study was to elucidate the interactions of human organic anion transporters (hOATs) and human organic cation transporters (hOCTs) with nonsteroidal anti-inflammatory drugs (NSAIDs) using cells stably expressing hOATs and hOCTs. NSAIDs tested were acetaminophen, acetylsalicylate, salicylate, diclofenac, ibuprofen, indomethacin, ketoprofen, mefenamic acid, naproxen, piroxicam, phenacetin, and sulindac. These NSAIDs inhibited organic anion uptake mediated by hOAT1, hOAT2, hOAT3, and hOAT4. By comparing the IC50 values of NSAIDs for hOATs, it was found that hOAT1 and hOAT3 exhibited higher affinity interactions with NSAIDs than did hOAT2 and hOAT4. HOAT1, hOAT2, hOAT3, and hOAT4 mediated the uptake of either ibuprofen, indomethacin, ketoprofen, or salicylate, but not acetylsalicylate. Although organic cation uptake mediated by hOCT1 and hOCT2 was also inhibited by some NSAIDs, hOCT1 and hOCT2 did not mediate the uptake of NSAIDs. In conclusion, hOATs and hOCTs interacted with various NSAIDs, whereas hOATs but not hOCTs mediated the transport of some of these NSAIDs. Considering the localization of hOATs, it was suggested that the interactions of hOATs with NSAIDs are associated with the pharmacokinetics and the induction of adverse reactions of NSAIDs.

Footnotes

  • DOI: 10.1124/jpet.102.037580

  • Abbreviations:
    NSAID
    nonsteroidal anti-inflammatory drug
    hOAT
    human organic anion transporter
    hOCT
    human organic cation transporter
    rOAT1
    rat organic anion transporter 1
    PGE2
    prostaglandin E2
    PGF2α
    prostaglandin F2α
    PAH
    para-aminohippuric acid
    S1
    S2, S3, the first, second, and third segments of the proximal tubule
    oatp
    organic anion-transporting peptide
    NPT1
    human-type I sodium-dependent inorganic phosphate transporter
    • Received April 15, 2002.
    • Accepted July 9, 2002.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 303 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 303, Issue 2
1 Nov 2002
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Research ArticleABSORPTION, DISTRIBUTION, METABOLISM, AND EXCRETION

Interactions of Human Organic Anion Transporters and Human Organic Cation Transporters with Nonsteroidal Anti-Inflammatory Drugs

Suparat Khamdang, Michio Takeda, Rie Noshiro, Shinichi Narikawa, Atsushi Enomoto, Naohiko Anzai, Pawinee Piyachaturawat and Hitoshi Endou
Journal of Pharmacology and Experimental Therapeutics November 1, 2002, 303 (2) 534-539; DOI: https://doi.org/10.1124/jpet.102.037580

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Research ArticleABSORPTION, DISTRIBUTION, METABOLISM, AND EXCRETION

Interactions of Human Organic Anion Transporters and Human Organic Cation Transporters with Nonsteroidal Anti-Inflammatory Drugs

Suparat Khamdang, Michio Takeda, Rie Noshiro, Shinichi Narikawa, Atsushi Enomoto, Naohiko Anzai, Pawinee Piyachaturawat and Hitoshi Endou
Journal of Pharmacology and Experimental Therapeutics November 1, 2002, 303 (2) 534-539; DOI: https://doi.org/10.1124/jpet.102.037580
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