Pharmacokinetic significance of renal OAT3 (SLC22A8) for anionic drug elimination in patients with mesangial proliferative glomerulonephritis.
OBJECTIVE
Our previous studies showed that the mRNA level of human organic anion transporter (hOAT) 3 in the kidney was correlated with the rate of elimination of an anionic antibiotic cefazolin. However, the correlation coefficient was not so high. In the present study, therefore, we enrolled more patients to examine whether additional factors were responsible for the correlation.


METHODS
hOAT mRNA levels in renal biopsy specimens were quantified using the real-time polymerase chain reaction method. The elimination rates for the free fraction of cefazolin were determined in patients with various renal diseases.


RESULTS
In the present study, the coefficient of correlation between the hOAT3 mRNA level and the elimination rates for the free fraction of cefazolin was not so high in the patients overall as in our previous study (r = 0.536). However, following the classification of renal diseases, a better correlation was obtained in patients with mesangial proliferative glomerulonephritis (r = 0.723). In contrast, multiple regression analyses including gender, age, and liver function did not result in any improvements in the correlation coefficients.


CONCLUSIONS
These results suggest that the hOAT3 mRNA level is a significant marker of pharmacokinetics with which to predict the rate of elimination of cefazolin in patients with mesangial proliferative glomerulonephritis.
Sakurai
Yuji
Y
Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Kyoto, Japan,
Motohashi
Hideyuki
H
Ogasawara
Ken
K
Terada
Tomohiro
T
Masuda
Satohiro
S
Katsura
Toshiya
T
Mori
Noriko
N
Matsuura
Motokazu
M
Doi
Toshio
T
Fukatsu
Atsushi
A
Inui
Ken-ichi
K
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000410:Alanine Transaminase / Q000097:blood; D000838:Anions / Q000378:metabolism; D001219:Aspartate Aminotransferases / Q000097:blood; D002437:Cefazolin / Q000493:pharmacokinetics; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D005838:Genotype; D015432:Glomerulonephritis, Membranoproliferative / Q000378:metabolism*; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D008875:Middle Aged; D029362:Organic Anion Transporters, Sodium-Independent / Q000378:metabolism*; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis
D000838:Anions; D018076:DNA, Complementary; D029362:Organic Anion Transporters, Sodium-Independent; D004364:Pharmaceutical Preparations; D012333:RNA, Messenger; C114338:organic anion transport protein 3; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D002437:Cefazolin