title: Comparison of pharmacokinetics and pathology for low-dose tacrolimus once-daily and twice-daily in living kidney transplantation: prospective trial in once-daily versus twice-daily tacrolimus.
abstract: BACKGROUND
  A prolonged-release formulation of tacrolimus (Tacrolimus QD) was developed to allow once-daily dosing and to have similar safety and efficacy profiles to twice-daily tacrolimus (Tacrolimus BID). This study compared the pharmacokinetics (PK) and renal pathology by protocol biopsy in de novo living kidney transplant recipients treated with either low-dose Tacrolimus QD or Tacrolimus BID.
  
  
  METHODS
  Between November 2009 and January 2011, 102 consecutive adult patients were randomized to receive either low-dose Tacrolimus QD or Tacrolimus BID. All patients underwent PK study and protocol biopsy on postoperative day 14. Additional protocol biopsies were performed between 6 and 12 months after renal transplantation.
  
  
  RESULTS
  During the 1-year follow up, the incidence of biopsy-proven acute rejection and toxic tubulopathy was low and similar in both groups. Twenty-four hours area under the curve (AUC0-24) was not different in both groups (285 ± 78.7 and 281 ± 62.4 ng hr/mL in Tacrolimus QD and Tacrolimus BID, respectively). C0 was well correlated with AUC0-24 in both groups and AUC0-24 between 260 and 280 in the Tacrolimus QD group was achieved by 6 to 8 ng/mL of C0. Acute nephrotoxicity was less than 10% in both groups without any clinical manifestation.
  
  
  CONCLUSIONS
  Clinical efficacy, safety, and PK profile of Tacrolimus QD is same as those of Tacrolimus BID.
authors.affiliation: Department of Urology, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Tsuchiya
authors.forename: Hideki
authors.initials: H
authors.lastname: Ishida
authors.forename: Tatsu
authors.initials: T
authors.lastname: Tanabe
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Shimizu
authors.forename: Kazuho
authors.initials: K
authors.lastname: Honda
authors.forename: Kazuya
authors.initials: K
authors.lastname: Omoto
authors.forename: Kazunari
authors.initials: K
authors.lastname: Tanabe
mesh_terms: D000208:Acute Disease; D000328:Adult; D003692:Delayed-Action Preparations; D004334:Drug Administration Schedule; D005260:Female; D006084:Graft Rejection / Q000473:pathology / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D007668:Kidney / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D016030:Kidney Transplantation / Q000473:pathology / Q000502:physiology; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016559:Tacrolimus / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D013997:Time Factors
chemical_list: D003692:Delayed-Action Preparations; D007166:Immunosuppressive Agents; D016559:Tacrolimus