title: Pharmacokinetic significance of renal OAT3 (SLC22A8) for anionic drug elimination in patients with mesangial proliferative glomerulonephritis.
abstract: 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.
authors.affiliation: Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Kyoto, Japan,
authors.forename: Yuji
authors.initials: Y
authors.lastname: Sakurai
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Motohashi
authors.forename: Ken
authors.initials: K
authors.lastname: Ogasawara
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Terada
authors.forename: Satohiro
authors.initials: S
authors.lastname: Masuda
authors.forename: Toshiya
authors.initials: T
authors.lastname: Katsura
authors.forename: Noriko
authors.initials: N
authors.lastname: Mori
authors.forename: Motokazu
authors.initials: M
authors.lastname: Matsuura
authors.forename: Toshio
authors.initials: T
authors.lastname: Doi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Fukatsu
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Inui
mesh_terms: 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
chemical_list: 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