title: Pharmacokinetics of tacrolimus converted from twice-daily formulation to once-daily formulation in Chinese stable liver transplant recipients.
abstract: OBJECTIVE
  To evaluate the pharmacokinetics of tacrolimus in Chinese stable liver transplant recipients converted from immediate release (IR) tacrolimus-based immunosuppression to modified release (MR) tacrolimus-based immunosuppression.
  
  
  METHODS
  Open-label, multi-center study with a one-way conversion design was conducted. Eighty-three stable liver recipients (6-24 months post-transplant) with normal renal and stable hepatic function were converted from IR tacrolimus twice-daily treatment to MR tacrolimus once-daily treatment on a 1:1 (mg: mg) total daily dose basis. Twenty-four hour pharmacokinetic studies were carried out on d 0 (pre-conversion), d 1, and d 84 (post-conversion).
  
  
  RESULTS
  The area under the blood concentration-time curve of MR tacrolimus from 0 to 24 h (AUC(0-24)) on d 1 was comparable to that of IR tacrolimus on d 0, with a 90% confidence interval (CI) for MR/IR tacrolimus of 92%-97%. The AUC(0-24) value for MR tacrolimus on d 84 with the daily dose increased by 14% was approximately 17% lower than that for IR tacrolimus. The 90% CI was 77%-90%, outside the bioequivalence range of 80%-125%. There was a good correlation between AUC(0-24) and concentration at 24 h (C(24)) for IR tacrolimus (d 0, r=0.930) and MR tacrolimus (d 1, r=0.936; d 84, r=0.903).
  
  
  CONCLUSIONS
  The exposure to tacrolimus when administered MR tacrolimus once daily is not equivalent to that for IR tacrolimus twice daily after an 84-day conversion in Chinese stable liver transplant recipients. The dose should be adjusted on the basis of trough levels. The therapeutic drug monitoring for patients treated with IR tacrolimus is considered to be applicable to MR tacrolimus.
authors.affiliation: Shanghai Institute of Materia Medica, Chinese Academy of Sciences, China.
authors.forename: Yi-fan
authors.initials: YF
authors.lastname: Zhang
authors.forename: Xiao-yan
authors.initials: XY
authors.lastname: Chen
authors.forename: Xiao-jian
authors.initials: XJ
authors.lastname: Dai
authors.forename: Xi-sheng
authors.initials: XS
authors.lastname: Leng
authors.forename: Da-fang
authors.initials: DF
authors.lastname: Zhong
mesh_terms: D000328:Adult; D000368:Aged; D002681:China; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000097:blood* / Q000627:therapeutic use; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D016559:Tacrolimus / Q000008:administration & dosage* / Q000097:blood* / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D016559:Tacrolimus