Expression levels of renal organic anion transporters (OATs) and their correlation with anionic drug excretion in patients with renal diseases.
OBJECTIVE
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.
Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan.
Yuji
Y
Sakurai
Hideyuki
H
Motohashi
Harumasa
H
Ueo
Satohiro
S
Masuda
Hideyuki
H
Saito
Masahiro
M
Okuda
Noriko
N
Mori
Motokazu
M
Matsuura
Toshio
T
Doi
Atsushi
A
Fukatsu
Osamu
O
Ogawa
Ken-ichi
K
Inui
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D002437:Cefazolin / Q000097:blood / Q000378:metabolism*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D007674:Kidney Diseases / Q000097:blood / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D027362:Organic Anion Transport Protein 1 / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D027361:Organic Anion Transporters / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D029362:Organic Anion Transporters, Sodium-Independent / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D004364:Pharmaceutical Preparations / Q000097:blood / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D014162:Transfection
D027362:Organic Anion Transport Protein 1; D027361:Organic Anion Transporters; D029362:Organic Anion Transporters, Sodium-Independent; D004364:Pharmaceutical Preparations; D012333:RNA, Messenger; C114338:organic anion transport protein 3; D002437:Cefazolin