title: Conversion from twice-daily to once-daily tacrolimus does not reduce intrapatient variability in tacrolimus exposure.
abstract: BACKGROUND
  Intrapatient variability (IPV) in tacrolimus exposure is associated with renal allograft failure. The aim of this study was to investigate whether conversion from the twice-daily tacrolimus formulation (Tac-TD) to a once-daily formulation (Tac-OD) leads to a lower IPV in tacrolimus exposure.
  
  
  METHODS
  Two hundred forty-seven stable renal transplant recipients were converted from Tac-TD to Tac-OD (Advagraf) on a 1:1-mg total daily dose basis. After conversion, patients were followed for 12 months and tacrolimus predose whole-blood concentrations (C0), serum creatinine, estimated glomerular filtration rate, and proteinuria were measured. These parameters were compared with those collected at all outpatient visits in the 12-month period (±3 months) before conversion (Tac-TD period). The IPV was calculated based on the dose-adjusted tacrolimus C0.
  
  
  RESULTS
  The Tac-OD formulation provided an excellent graft survival (100%), a low acute rejection rate (0.8%), and good tolerability. Renal function remained stable: estimated glomerular filtration rate 48 (16-90) versus 46 (12-90) mL/min (P = 0.15) before and after conversion, respectively. After conversion to Tac-OD, mean C0 was significantly lower, decreasing from 5.7 ± 1.5 to 5.0 ± 1.5 ng/mL, corresponding to a 12% reduction (P < 0.01). Both drugs had similar IPVs (Tac-TD: 17.3% ± 1.6% versus Tac-OD: 16.4% ± 1.6%, P = 0.31).
  
  
  CONCLUSIONS
  Although conversion from Tac-TD to Tac-OD significantly reduces tacrolimus exposure as measured by C0 and seems safe, it does not reduce IPV in tacrolimus exposure.
authors.affiliation: *Department of Hospital Pharmacy, Clinical Pharmacology Unit; and †Department of Internal Medicine, Division of Nephrology and Renal Transplantation, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
authors.forename: Nauras
authors.initials: N
authors.lastname: Shuker
authors.forename: Monique
authors.initials: M
authors.lastname: Cadogan
authors.forename: Teun
authors.initials: T
authors.lastname: van Gelder
authors.forename: Joke I
authors.initials: JI
authors.lastname: Roodnat
authors.forename: Marcia M L
authors.initials: MM
authors.lastname: Kho
authors.forename: Willem
authors.initials: W
authors.lastname: Weimar
authors.forename: Dennis A
authors.initials: DA
authors.lastname: Hesselink
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004334:Drug Administration Schedule; D005260:Female; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D016559:Tacrolimus / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D016559:Tacrolimus