title: Conversion from Prograf to Advagraf among kidney transplant recipients results in sustained decrease in tacrolimus exposure.
abstract: BACKGROUND
  Advagraf is a slow release form of tacrolimus with once-daily formulation. The potential advantages of Advagraf are better adherence and a safer profile by avoiding toxic peak concentrations. In this study, we evaluated the required daily doses of tacrolimus and subsequent blood levels on conversion from Prograf to Advagraf among kidney transplant recipients.
  
  
  METHODS
  We retrospectively reviewed data from 55 patients for whom a switch from Prograf to Advagraf was identified. Tacrolimus daily doses and concomitant blood levels were analyzed at several time points ranging from 3 months before to 6 months after conversion.
  
  
  RESULTS
  We observed a significant increase in tacrolimus daily doses, starting with a dose of 0.063 mg/kg of Prograf, increasing up to 0.081 mg/kg of Advagraf at 6 months (P<0.0001). After conversion, we observed a quick and sustained decrease in trough tacrolimus levels, decreasing from 8.05 ng/mL at day 0 to 6.30 ng/mL at day 180 (P=0.0009). At 6 months, 35% of patients experienced a decrease in trough levels of more than 30%. Creatinine values remained stable over time, and no patient experienced an acute rejection episode.
  
  
  CONCLUSIONS
  Contrary to the manufacturer instructions, we found a significant decrease in tacrolimus exposure after switching to Advagraf. Therefore, the switch from Prograf to Advagraf should be performed under close medical supervision.
authors.affiliation: Renal Transplantation Clinic, Department of Nephrology, Clinique Universitaire Hôpital Erasme, 808 Route de Lennik, Brussels, Belgium. jehougar@ulb.ac.be
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Hougardy
authors.forename: Nilufer
authors.initials: N
authors.lastname: Broeders
authors.forename: Mireille
authors.initials: M
authors.lastname: Kianda
authors.forename: Annick
authors.initials: A
authors.lastname: Massart
authors.forename: Phillippe
authors.initials: P
authors.lastname: Madhoun
authors.forename: Alain
authors.initials: A
authors.lastname: Le Moine
authors.forename: Anh-Dung
authors.initials: AD
authors.lastname: Hoang
authors.forename: Dimitri
authors.initials: D
authors.lastname: Mikhalski
authors.forename: Karl M
authors.initials: KM
authors.lastname: Wissing
authors.forename: Daniel
authors.initials: D
authors.lastname: Abramowicz
mesh_terms: D000328:Adult; D000368:Aged; D002626:Chemistry, Pharmaceutical; D003404:Creatinine / Q000097:blood; D003430:Cross-Sectional Studies; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000097:blood / Q000627:therapeutic use; D007668:Kidney / Q000502:physiology; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D008991:Monitoring, Physiologic; D012189:Retrospective Studies; D016559:Tacrolimus / Q000008:administration & dosage* / Q000097:blood / Q000627:therapeutic use
chemical_list: D007166:Immunosuppressive Agents; D003404:Creatinine; D016559:Tacrolimus