Interactions of Human- and Rat-Organic Anion Transporters With Pravastatin and Cimetidine

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  • Khamdang Suparat
    Department of Pharmacology and Toxicology, Kyorin University School of Medicine Department of Physiology, Faculty of Science, Mahidol University
  • Takeda Michio
    Department of Pharmacology and Toxicology, Kyorin University School of Medicine
  • Shimoda Minoru
    Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology
  • Noshiro Rie
    Department of Pharmacology and Toxicology, Kyorin University School of Medicine
  • Narikawa Shinichi
    Kobuchizawa Laboratories, Fuji Biomedixs Co.
  • Huang Xiu-Lin
    Kobuchizawa Laboratories, Fuji Biomedixs Co.
  • Enomoto Atsushi
    Department of Pharmacology and Toxicology, Kyorin University School of Medicine
  • Piyachaturawat Pawinee
    Department of Physiology, Faculty of Science, Mahidol University
  • Endou Hitoshi
    Department of Pharmacology and Toxicology, Kyorin University School of Medicine

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Abstract

We have elucidated the interactions of human and rat organic anion transporters (hOATs and rOATs) with pravastatin and cimetidine. Pravastatin inhibited hOAT1/rOAT1, hOAT2/rOAT2, hOAT3/rOAT3, and hOAT4. The mode of inhibition was noncompetitive for hOAT1 and hOAT2, whereas it was competitive for hOAT3 and hOAT4. Cimetidine also inhibited hOAT1/rOAT1, hOAT3/rOAT3, and hOAT4. The mode of inhibition was a combination of competitive and noncompetitive manners for hOAT1, whereas it was competitive for hOAT3. The effects of OAT inhibitors on OAT1, OAT2, and OAT3 exhibited some but not so remarkable interspecies differences between humans and rats. In conclusion, we have characterized pravastatin and cimetidine as OAT inhibitors.<br>

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