title: A limited sampling strategy to estimate the area under the concentration-time curve of tacrolimus modified-release once-daily preparation in renal transplant recipients.
abstract: OBJECTIVE
  The aim of this study was to develop a limited sampling strategy to estimate the area under the concentration-time curve (AUC) of a modified-release, once-daily formulation of tacrolimus (Advagraf, Japanese trade name Graceptor) with Japanese renal transplant patients.
  
  
  METHODS
  Among the 43 enrolled patients, 23 patients continued to take Graceptor for 1 year. A total of 66 profiles on day 28 and day 365 from the 43 patients were randomly divided into a training group (N = 33) and a validation group (N = 33) without any overlap.
  
  
  RESULTS
  The prediction formula for the AUC 0-24 using the single C 12h time point gave the highest correlation with the observed AUC 0-24 (r2 = 0.9057). When 2 sampling times were used, C 0h-C 12h were the best time points for the estimation of the AUC 0-24 (AUC 0-24 = 26.8 + 8.0C 0h + 17.8C 12h, r2 = 0.9221, P < 0.0001). There was no significant difference in the prediction error for the prediction formulas with the C 0h-C 12h combination between CYP3A5 genotypes. The % mean prediction error, % mean absolute error, and % root mean squared prediction error of the prediction formula using C 0h-C 12h were 0.1%, 7.6%, and 8.8%, respectively.
  
  
  CONCLUSIONS
  In a hospital setting, a limited sampling strategy using C 0h-C 12h would be applicable to estimating the AUC 0-24 of tacrolimus once daily.
authors.affiliation: Department of Pharmacy, Akita University Hospital, Akita, Japan.
authors.forename: Takenori
authors.initials: T
authors.lastname: Niioka
authors.forename: Masatomo
authors.initials: M
authors.lastname: Miura
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kagaya
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Saito
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Numakura
authors.forename: Tomonori
authors.initials: T
authors.lastname: Habuchi
authors.forename: Shigeru
authors.initials: S
authors.lastname: Satoh
mesh_terms: D000328:Adult; D000368:Aged; D019540:Area Under Curve; D002626:Chemistry, Pharmaceutical; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism*; D016030:Kidney Transplantation / Q000379:methods*; D008297:Male; D008875:Middle Aged; D016559:Tacrolimus / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism*; D013997:Time Factors; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D016559:Tacrolimus