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• W2000788611 abstract "You have accessJournal of UrologyTransplantation & Vascular Surgery: Renal Transplantation, Vascular Surgery II1 Apr 20122262 PERSONALIZED INITIAL DOSE OF TACROLIMUS BASED ON THE CYP3A5 POLYMORPHISM AND ITS IMPACT ON THE 1-MONTH GRAFT FUNCTION: A PRELIMINARY EXPERIENCE Shigeru Satoh, Kazuyuki Numakura, Yoshiko Miura, Mitsuru Saito, Shinya Maita, Takashi Obara, Takamitsu Inoue, Shintaro Narita, Yohei Horikawa, Norihiko Tsuchiya, Tomonori Habuchi, Hideaki Kagaya, and Masatomo Miura Shigeru SatohShigeru Satoh Akita, Japan More articles by this author , Kazuyuki NumakuraKazuyuki Numakura Akita, Japan More articles by this author , Yoshiko MiuraYoshiko Miura Akita, Japan More articles by this author , Mitsuru SaitoMitsuru Saito Akita, Japan More articles by this author , Shinya MaitaShinya Maita Akita, Japan More articles by this author , Takashi ObaraTakashi Obara Akita, Japan More articles by this author , Takamitsu InoueTakamitsu Inoue Akita, Japan More articles by this author , Shintaro NaritaShintaro Narita Akita, Japan More articles by this author , Yohei HorikawaYohei Horikawa Akita, Japan More articles by this author , Norihiko TsuchiyaNorihiko Tsuchiya Akita, Japan More articles by this author , Tomonori HabuchiTomonori Habuchi Akita, Japan More articles by this author , Hideaki KagayaHideaki Kagaya Akita, Japan More articles by this author , and Masatomo MiuraMasatomo Miura Akita, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.2440AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES 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 target trough levels (C0) (Tsuchiya, Transplantation, 2004). Recently, we reported that renal cortical interstitial fibrosis (IF) from 0-hour to 1-year post-transplantation increased in non-expressers than CYP3A5 expressers. Unexpected highly tacrolimus levels in non-expressers might influence the development of IF, despite therapeutic drug monitoring (Miura, Transplantation 2011). Therefore, since January 2011, we have started to a personalized initial dosing regimen of controlled-release tacrolimus based on the CYP3A5 polymorphism. The present study investigated the impact of personalized regimen of tacrolimus on the pharmacokinetics and 1-month graft function comparing to the non-personalized regimen. METHODS Initial oral doses of tacrolimus were 0.20mg/kg for CYP3A5 expressers and 0.10mg/kg for non-expressers. In the non-personalized regimen, all patients received 0.20mg/kg of tacrolimus. The target trough levels of tacrolimus were same between the two regimes. RESULTS Twenty patients were involved in the personalized regimen; CYP3A5 expressers in 6 and non-expressers in 14 cases. Twenty-five patients were in involved in the non-personalized regimen; CYP3A5 expressers in 10 and non-expressers in 15 cases. In the non-personalized regimen, C0 and area under the blood concentration-time curve (AUC) of tacrolimus and estimated glomerular filtration rate (eGFR) in CYP3A5 expressers and non-expressers were: C0 (4.8 vs. 8.5 ng/ml, p=0.001) and AUC (218 vs. 373 nghr/ml, p=0.001) at day 1 after first administration of tacrolimus, C0 (5.4 vs 7.8 ng/ml, p=0.004) and AUC (218 vs 287 nghr/ml, p=0.013) and eGFR (59.2 vs 42.4 ml/min/1.73m2, p=0.028) at day 28 post-transplantation. In the personalized regimen, C0 and AUC of tacrolimus and eGFR in CYP3A5 expressers and non-expressers were; C0 (6.9 vs 2.7 ng/ml, p=0.279) and AUC (377 vs 136 nghr/ml, p=0.268) at day 1, C0 (8.9 vs 5.2 ng/mL, p=0.0270) and AUC (332 vs 226 nghr/mL, p=0.073) and eGFR (47.7 vs 64.6 ml/min/1.73m2, p=0.202) at day 28. CONCLUSIONS The personalized medicine of tacrolimus based on the CYP3A5 polymorphism may decrease the pharmacokinetic difference between CYP3A5 expressers and non-expressers, and it may contribute better graft function in non-expressers in the early post-transplantation. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e913 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Shigeru Satoh Akita, Japan More articles by this author Kazuyuki Numakura Akita, Japan More articles by this author Yoshiko Miura Akita, Japan More articles by this author Mitsuru Saito Akita, Japan More articles by this author Shinya Maita Akita, Japan More articles by this author Takashi Obara Akita, Japan More articles by this author Takamitsu Inoue Akita, Japan More articles by this author Shintaro Narita Akita, Japan More articles by this author Yohei Horikawa Akita, Japan More articles by this author Norihiko Tsuchiya Akita, Japan More articles by this author Tomonori Habuchi Akita, Japan More articles by this author Hideaki Kagaya Akita, Japan More articles by this author Masatomo Miura Akita, Japan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ..." @default.
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• W2000788611 title "2262 PERSONALIZED INITIAL DOSE OF TACROLIMUS BASED ON THE CYP3A5 POLYMORPHISM AND ITS IMPACT ON THE 1-MONTH GRAFT FUNCTION: A PRELIMINARY EXPERIENCE" @default.
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