title: Delayed bottom-up and amended simple method of dosing with once-daily tacrolimus application to achieve stable trough levels in liver transplantation.
abstract: BACKGROUND
  Tacrolimus once-daily formulation (TacOD) was introduced as an alternative to twice-daily formulations de novo. Dosing recommendations range between 0.1 to 0.2 mg/kg BW/d.
  
  
  METHODS
  Amended dosing with a simple bottom-up de novo algorithm is presented. Primary outcome measure was feasibility of establishing adequate target trough levels and avoidance of over-immunosuppression, with adequate safety and efficacy after liver transplantation (LT).
  
  
  RESULTS
  TacOD was given to 101 patients. Standard steroid-free immunosuppression consisted of MMF 2 g/d, basiliximab 20 mg on day 0 and 4, and delayed bottom-up IS with TacOD starting with 1 mg/d and doubling the dosage every day until target trough levels of 5 to 8 ng/ml were reached. By day 7 after LT, all except 3 patients had received TacOD. The earliest time point of introduction was day 2. A median of 9 mg/d (range: 0 to 25 mg/d) of TacOD were necessary to establish the trough levels by day 10, which was then 5.4 ng/ml (range: 1.5 to 20 ng/ml). Incidence of adverse events (AE), in particular neurological AEs (n=3), were low. Efficacy failure (acute rejection) was low (4.9%). Renal function was stable and did not deteriorate under CNI treatment.
  
  
  CONCLUSIONS
  This is the first report of bottom-up, amended, and simple dosing of TacOD in LT. The algorithm is feasible, safe, and efficient, avoiding trough level peaks and top-down strategies.
authors.affiliation: Department of General and Visceral Surgery, Frankfurt University Hospitals, Goethe University Frankfurt/Main, Frankfurt/Main, Germany.
authors.forename: Andreas A
authors.initials: AA
authors.lastname: Schnitzbauer
authors.affiliation: Department of General and Visceral Surgery, Frankfurt University Hospitals, Goethe University Frankfurt/Main, Frankfurt/Main, Germany.
authors.forename: Ceylan
authors.initials: C
authors.lastname: Ayik
authors.affiliation: Department of General and Visceral Surgery, Frankfurt University Hospitals, Goethe University Frankfurt/Main, Frankfurt/Main, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Ulrich
authors.affiliation: Department of General and Visceral Surgery, Frankfurt University Hospitals, Goethe University Frankfurt/Main, Frankfurt/Main, Germany.
authors.forename: Wolf O
authors.initials: WO
authors.lastname: Bechstein
authors.affiliation: Department of General and Visceral Surgery, Frankfurt University Hospitals, Goethe University Frankfurt/Main, Frankfurt/Main, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Mönch
mesh_terms: D000328:Adult; D000368:Aged; D004334:Drug Administration Schedule; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods*; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D016031:Liver Transplantation / Q000379:methods*; D008297:Male; D008875:Middle Aged; D016559:Tacrolimus / Q000008:administration & dosage* / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D016559:Tacrolimus