@article{oai:hirosaki.repo.nii.ac.jp:00003773,
 author = {Satoh, Shigeru and Saito, Mitsuru and Numakura, Kazuyuki and Miura, Yoshio and Inoue, Takamitsu and Maita, Shinya and Obara, Takashi and Tsuruta, Hiroshi and Narita, Shintaro and Horikawa, Yohei and Tsuchiya, Norihiko and Habuchi, Tomonori and Mitobe, Yoko and Komatsuda, Atsushi and Kagaya, Hideaki and Miura, Masatomo},
 issue = {Supplement},
 journal = {弘前医学},
 month = {Apr},
 note = {Since January 2011, we have started to a personalized medicine for controlled-release tacrolimus, once-daily oral formulation of tacrolimus, based on the CYP3A5 polymorphisms. Tacrolimus has a narrow therapeutic range, and its pharmacokinetics differs greatly among individuals. Many factors may affect the pharmacokinetics of tacrolimus, including CYP3A5 genotypes. Patients with CYP3A5*1 allele（ CYP3A5 expressers） require a higher daily tacrolimus dose than those with CYP3A5*3/*3 genotype （non-expressers） in order to maintain the target trough level. Recently, we investigated the increase in renal cortical interstitial fibrosis （IF） from 0-hour to 1-year posttransplantation using an automated digital analysis of biopsy sections and assessed the relative risk of developing IF based on clinical characteristics, laboratory data, tacrolimus-based immunosuppressive regimens, and the CYP3A5 polymorphism. In a multivariate analysis, CYP3A5 non-expression correlated with the development of IF. The mean tacrolimus trough concentrations in the early stages after transplantation were unexpectedly higher among non-expressers than CYP3A5 expressers, despite therapeutic drug monitoring. This unexpectedly high tacrolimus levels in non-expressers might influence the development of IF.
　 Before staring the personalize medicine for controlled-release tacrolimus, we analyzed circadian pharmacokinetics and pharmacogenetics of twice daily tacrolimus, and its association with transplant outcome. We briefly reviewed our clinical research into tacrolimus., 弘前医学. 64(Suppl.), 2013, p.S19-27},
 pages = {S19--S27},
 title = {Pharmacogenetics and Circadian exposure of Tacrolimus and Its Impact on the renal Transplant Outcome: A Way to a Personalized Medicine for Tacrolimus},
 volume = {64},
 year = {2013}
}