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

Yuji Sakurai, Hideyuki Motohashi, Harumasa Ueo, Satohiro Masuda, Hideyuki Saito, Masahiro Okuda, Noriko Mori, Motokazu Matsuura, Toshio Doi, Atsushi Fukatsu, Osamu Ogawa, Ken Ichi Inui

Research output: Contribution to journalArticle

73 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)61-67
Number of pages7
JournalPharmaceutical Research
Volume21
Issue number1
DOIs
Publication statusPublished - Jan 1 2004

Fingerprint

Organic Anion Transporters
Cefazolin
Kidney
Pharmaceutical Preparations
Phenolsulfonphthalein
Messenger RNA
Drug-Related Side Effects and Adverse Reactions
Polymerase chain reaction
Real-Time Polymerase Chain Reaction

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)

Cite this

Expression Levels of Renal Organic Anion Transporters (OATs) and Their Correlation with Anionic Drug Excretion in Patients with Renal Diseases. / Sakurai, Yuji; Motohashi, Hideyuki; Ueo, Harumasa; Masuda, Satohiro; Saito, Hideyuki; Okuda, Masahiro; Mori, Noriko; Matsuura, Motokazu; Doi, Toshio; Fukatsu, Atsushi; Ogawa, Osamu; Inui, Ken Ichi.

In: Pharmaceutical Research, Vol. 21, No. 1, 01.01.2004, p. 61-67.

Research output: Contribution to journalArticle

Sakurai, Y, Motohashi, H, Ueo, H, Masuda, S, Saito, H, Okuda, M, Mori, N, Matsuura, M, Doi, T, Fukatsu, A, Ogawa, O & Inui, KI 2004, 'Expression Levels of Renal Organic Anion Transporters (OATs) and Their Correlation with Anionic Drug Excretion in Patients with Renal Diseases', Pharmaceutical Research, vol. 21, no. 1, pp. 61-67. https://doi.org/10.1023/B:PHAM.0000012153.71993.cb
Sakurai, Yuji ; Motohashi, Hideyuki ; Ueo, Harumasa ; Masuda, Satohiro ; Saito, Hideyuki ; Okuda, Masahiro ; Mori, Noriko ; Matsuura, Motokazu ; Doi, Toshio ; Fukatsu, Atsushi ; Ogawa, Osamu ; Inui, Ken Ichi. / Expression Levels of Renal Organic Anion Transporters (OATs) and Their Correlation with Anionic Drug Excretion in Patients with Renal Diseases. In: Pharmaceutical Research. 2004 ; Vol. 21, No. 1. pp. 61-67.
@article{a989cc3d2d4f47de8f2ff9c9498a7edd,
title = "Expression Levels of Renal Organic Anion Transporters (OATs) and Their Correlation with Anionic Drug Excretion in Patients with Renal Diseases",
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.",
author = "Yuji Sakurai and Hideyuki Motohashi and Harumasa Ueo and Satohiro Masuda and Hideyuki Saito and Masahiro Okuda and Noriko Mori and Motokazu Matsuura and Toshio Doi and Atsushi Fukatsu and Osamu Ogawa and Inui, {Ken Ichi}",
year = "2004",
month = "1",
day = "1",
doi = "10.1023/B:PHAM.0000012153.71993.cb",
language = "English",
volume = "21",
pages = "61--67",
journal = "Pharmaceutical Research",
issn = "0724-8741",
publisher = "Springer New York",
number = "1",

}

TY - JOUR

T1 - Expression Levels of Renal Organic Anion Transporters (OATs) and Their Correlation with Anionic Drug Excretion in Patients with Renal Diseases

AU - Sakurai, Yuji

AU - Motohashi, Hideyuki

AU - Ueo, Harumasa

AU - Masuda, Satohiro

AU - Saito, Hideyuki

AU - Okuda, Masahiro

AU - Mori, Noriko

AU - Matsuura, Motokazu

AU - Doi, Toshio

AU - Fukatsu, Atsushi

AU - Ogawa, Osamu

AU - Inui, Ken Ichi

PY - 2004/1/1

Y1 - 2004/1/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=1642539149&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=1642539149&partnerID=8YFLogxK

U2 - 10.1023/B:PHAM.0000012153.71993.cb

DO - 10.1023/B:PHAM.0000012153.71993.cb

M3 - Article

VL - 21

SP - 61

EP - 67

JO - Pharmaceutical Research

JF - Pharmaceutical Research

SN - 0724-8741

IS - 1

ER -