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Expression Levels of Renal Organic Anion Transporters (OATs) and Their Correlation with Anionic Drug Excretion in Patients with Renal Diseases

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Abstract

Purpose. Because the urinary excretion of drugs is often decreased in renal diseases, dosage regimens are adjusted to avoid adverse drug reactions. The aim of present study was to clarify the alteration in the levels of renal drug transporters and their correlation with the urinary drug excretion in renal diseases patients.

Methods. We quantified the mRNA levels of human organic anion transporters (hOATs) by real-time polymerase chain reaction and examined the excretion of the anionic drug, cefazolin, in renal disease patients. Moreover, transport of cefazolin by hOAT1 and hOAT3 were examined using HEK293 transfectants.

Results. Among four hOATs, the level of hOAT1 mRNA was significantly lower in the kidney of patients with renal diseases than in the normal controls. The elimination constant of cefazolin showed a significant correlation with the values of phenolsulfonphthalein test and mRNA levels of hOAT3. The uptake study using HEK293 transfectants revealed that cefazolin and phenolsulfonphthalein were transported by hOAT3.

Conclusions. These results suggest that hOAT3 plays an important role for anionic drug secretion in patients with renal diseases and that the expression levels of drug transporters may be related to the alteration of renal drug secretion.

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Authors and Affiliations

  1. Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Sakyo-ku, Kyoto, 606-8507, Japan

    Yuji Sakurai, Hideyuki Motohashi, Harumasa Ueo, Satohiro Masuda, Hideyuki Saito, Masahiro Okuda & Ken-ichi Inui

  2. Department of Nephrology, Shizuoka Prefectural Hospital, Shizuoka, Japan

    Noriko Mori

  3. Department of Clinical Biology and Medicine, University of Tokushima, Tokushima, Japan

    Motokazu Matsuura & Toshio Doi

  4. Division of Artificial Kidneys, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Sakyo-ku, Kyoto, 606-8507, Japan

    Atsushi Fukatsu

  5. Department of Urology, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Sakyo-ku, Kyoto, 606-8507, Japan

    Osamu Ogawa

Authors
  1. Yuji Sakurai
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  2. Hideyuki Motohashi
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  3. Harumasa Ueo
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  4. Satohiro Masuda
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  5. Hideyuki Saito
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  10. Atsushi Fukatsu
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  11. Osamu Ogawa
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  12. Ken-ichi Inui
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Correspondence to Ken-ichi Inui.

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Sakurai, Y., Motohashi, H., Ueo, H. et al. Expression Levels of Renal Organic Anion Transporters (OATs) and Their Correlation with Anionic Drug Excretion in Patients with Renal Diseases. Pharm Res 21, 61–67 (2004). https://doi.org/10.1023/B:PHAM.0000012153.71993.cb

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  • DOI: https://doi.org/10.1023/B:PHAM.0000012153.71993.cb

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