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
N1 - Funding Information:
This work was supported by a grant-in-aid for Research on Human Genome, Tissue Engineering and Food Biotechnology from the Ministry of Health, Labor and Welfare of Japan (H12-Genome-019) and a grant-in-aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan.
PY - 2004/1
Y1 - 2004/1
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.
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U2 - 10.1023/B:PHAM.0000012153.71993.cb
DO - 10.1023/B:PHAM.0000012153.71993.cb
M3 - Article
C2 - 14984259
AN - SCOPUS:1642539149
SN - 0724-8741
VL - 21
SP - 61
EP - 67
JO - Pharmaceutical Research
JF - Pharmaceutical Research
IS - 1
ER -
