title: Influence of everolimus on the pharmacokinetics of tacrolimus in Japanese renal transplant patients.
abstract: To examine whether a trough concentration of everolimus in the therapeutic range of 3-5 ng/mL affects the pharmacokinetics of tacrolimus in renal transplant patients.
  
  
  
  A total of 52 Japanese renal transplant patients receiving tacrolimus were enrolled in this study. In 28 of them, everolimus was co-administered on day 14 after surgery. Changes in the dose-adjusted blood trough concentration of tacrolimus from day 14 to 28 after surgery were investigated.
  
  
  
  The dose-adjusted blood trough concentration of tacrolimus on day 28 was affected by CYP3A5*3/*3 and hemoglobin level (P < 0.001 and P = 0.007), but not by everolimus (P = 0.171). In addition, there was no change in the dose-adjusted blood trough concentration of tacrolimus in patients before or after everolimus coadministration (P = 0.165). On day 28, there was no correlation between the rate of change in the dose-adjusted blood trough concentration of tacrolimus and the blood trough concentration or area under the plasma concentration-time curve from 0 to 12 h for everolimus after initiation of combination therapy (r = 0.341, P = 0.076 and r = 0.234, P = 0.231).
  
  
  
  A pharmacokinetic interaction between tacrolimus and everolimus was not observed clinically in renal transplant patients. Safe and reliable immunosuppressive therapy in renal transplant patients might be achieved using a combination of tacrolimus and everolimus.
authors.affiliation: Department of Pharmacy, Akita University Hospital, Akita, Japan.
authors.forename: Takenori
authors.initials: T
authors.lastname: Niioka
authors.affiliation: Department of Pharmacy, Akita University Hospital, Akita, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kagaya
authors.affiliation: Department of Urology, Akita University School of Medicine, Akita, Japan.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Saito
authors.affiliation: Department of Urology, Akita University School of Medicine, Akita, Japan.
authors.forename: Takamitsu
authors.initials: T
authors.lastname: Inoue
authors.affiliation: Department of Urology, Akita University School of Medicine, Akita, Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Numakura
authors.affiliation: Department of Urology, Akita University School of Medicine, Akita, Japan.
authors.forename: Ryohei
authors.initials: R
authors.lastname: Yamamoto
authors.affiliation: Department of Pharmacy, Akita University Hospital, Akita, Japan.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Akamine
authors.affiliation: Department of Urology, Akita University School of Medicine, Akita, Japan.
authors.forename: Tomonori
authors.initials: T
authors.lastname: Habuchi
authors.affiliation: Center for Kidney Disease and Transplantation, Akita University Hospital, Akita, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Satoh
authors.affiliation: Department of Pharmacy, Akita University Hospital, Akita, Japan.
authors.forename: Masatomo
authors.initials: M
authors.lastname: Miura
mesh_terms: D019540:Area Under Curve; D051544:Cytochrome P-450 CYP3A; D000068338:Everolimus / Q000494:pharmacology*; D005838:Genotype; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics* / Q000494:pharmacology; D016030:Kidney Transplantation; D016559:Tacrolimus / Q000493:pharmacokinetics*
chemical_list: D007166:Immunosuppressive Agents; D000068338:Everolimus; D051544:Cytochrome P-450 CYP3A; D016559:Tacrolimus
keywords: CYP3A5 genotype; everolimus; pharmacokinetic interaction; renal transplantation; tacrolimus