title: Pharmacokinetic and CYP3A5 pharmacogenetic differences between once- and twice-daily tacrolimus from the first dosing day to 1 year after renal transplantation.
abstract: Aim & patients & methods: This study investigated 24-h pharmacokinetic and CYP3A5 pharmacogenetic differences between once-daily tacrolimus (Tac-q.d.) versus twice-daily tacrolimus (Tac-b.i.d.) pretransplantation and at 1 month and 1 year post-transplantaion.
  
  
  RESULTS
  The dose-adjusted trough level (Cmin) and area under the blood concentration-time curve from 0 to 24 h (AUC₀₋₂₄) increased twofold within 1 year post-transplantation with both formulations and the two genotypes. Good correlations were observed between the AUC₀₋₂₄ and Cmin for both formulations. However, the dose-adjusted Cmin, but not dose-adjusted AUC₀₋₂₄, was approximately 30% lower for Tac-q.d. than for Tac-b.i.d. Although the dose-adjusted Cmin was lower for Tac-q.d. than for Tac-b.i.d. in both genotypes, the dose-adjusted AUC₀₋₂₄ was approximately 25% lower for Tac-q.d. than for Tac-b.i.d. in CYP3A5 expressers, but not in nonexpressers during the study period.
  
  
  CONCLUSIONS
  These results suggested that the approximately 30% lower Cmin for Tac-q.d. than for Tac-b.i.d. may have achieved the same AUC₀₋₂₄ with both formulations and may be associated with CYP3A5 pharmacogenomic differences, especially in CYP3A5 expressers, between Tac-b.i.d. and Tac-q.d.
authors.affiliation: Center for Kidney Disease & Transplantation, Akita University School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Satoh
authors.forename: Takenori
authors.initials: T
authors.lastname: Niioka
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kagaya
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Numakura
authors.forename: Takamitsu
authors.initials: T
authors.lastname: Inoue
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Saito
authors.forename: Naoki
authors.initials: N
authors.lastname: Komine
authors.forename: Shintaro
authors.initials: S
authors.lastname: Narita
authors.forename: Norihiko
authors.initials: N
authors.lastname: Tsuchiya
authors.forename: Tomonori
authors.initials: T
authors.lastname: Habuchi
authors.forename: Masatomo
authors.initials: M
authors.lastname: Miura
mesh_terms: D000328:Adult; D000368:Aged; D019540:Area Under Curve; D051544:Cytochrome P-450 CYP3A / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D016030:Kidney Transplantation / Q000379:methods; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics / Q000379:methods; D011110:Polymorphism, Genetic / Q000235:genetics*; D012189:Retrospective Studies; D016559:Tacrolimus / Q000008:administration & dosage*; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; D016559:Tacrolimus
keywords: Advagraf; CYP3A5 6986A>G; Prograf; pharmacogenomics; pharmacokinetics; tacrolimus