title: Capability of utilizing CYP3A5 polymorphisms to predict therapeutic dosage of tacrolimus at early stage post-renal transplantation.
abstract: While CYP3A5 polymorphisms are used to predict the initial dosage of tacrolimus therapy, the predictive capability of genetic information for dosing at early stage post-renal transplantation is unknown. We investigated the influence of polymorphisms over time. An initial oral dose of modified-release once-daily tacrolimus formulation (0.20 mg/kg) was administered to 50 Japanese renal transplant patients every 24 h. Stepwise multiple linear regression analysis for tacrolimus dosing was performed each week to determine the effect of patient clinical characteristics. The dose-adjusted trough concentration was approximately 70% higher for patients with the CYP3A5*3/*3 than patients with the CYP3A5*1 allele before the second pre-transplantation tacrolimus dose (0.97 (0.78-1.17) vs. 0.59 (0.45-0.87) ng/mL/mg; p < 0.001). The contribution of genetic factors (CYP3A5*1 or *3) for tacrolimus dosing showed increased variation from Day 14 to Day 28 after transplantation: 7.2%, 18.4% and 19.5% on Days 14, 21 and 28, respectively. The influence of CYP3A5 polymorphisms on the tacrolimus maintenance dosage became evident after Day 14 post-transplantation, although the tacrolimus dosage was determined based only on patient body weight for the first three days after surgery. Tacrolimus dosage starting with the initial administration should be individualized using the CYP3A5 genotype information.
authors.affiliation: Department of Pharmacy, Akita University Hospital, 1-1-1 Hondo, Akita 010-8543, Japan. tniio-hki@umin.ac.jp.
authors.forename: Takenori
authors.initials: T
authors.lastname: Niioka
authors.affiliation: Department of Pharmacy, Akita University Hospital, 1-1-1 Hondo, Akita 010-8543, Japan. hideaki-kagaya@hos.akita-u.ac.jp.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kagaya
authors.affiliation: Department of Urology, Akita University School of Medicine, Akita 010-8543, Japan. urosaito@gmail.com.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Saito
authors.affiliation: Department of Urology, Akita University School of Medicine, Akita 010-8543, Japan. takmitz@gmail.com.
authors.forename: Takamitsu
authors.initials: T
authors.lastname: Inoue
authors.affiliation: Department of Urology, Akita University School of Medicine, Akita 010-8543, Japan. nqf38647@nifty.com.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Numakura
authors.affiliation: Department of Urology, Akita University School of Medicine, Akita 010-8543, Japan. thabuchi@gmail.com.
authors.forename: Tomonori
authors.initials: T
authors.lastname: Habuchi
authors.affiliation: Center for Kidney Disease and Transplantation, Akita University Hospital, Akita 010-8543, Japan. shigerus@doc.med.akita-u.ac.jp.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Satoh
authors.affiliation: Department of Pharmacy, Akita University Hospital, 1-1-1 Hondo, Akita 010-8543, Japan. m-miura@hos.akita-u.ac.jp.
authors.forename: Masatomo
authors.initials: M
authors.lastname: Miura
mesh_terms: D000328:Adult; D000368:Aged; D051544:Cytochrome P-450 CYP3A / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005838:Genotype; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012189:Retrospective Studies; D016559:Tacrolimus / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; D016559:Tacrolimus