title: A prospective cohort conversion study of twice-daily to once-daily extended-release tacrolimus: role of ethnicity.
abstract: BACKGROUND
  Tacrolimus is a widely used calcineurin inhibitor in kidney transplantation. It is available as twice-daily Prograf® (Tac-BID) and once-daily Advagraf® (Tac-OD). Although therapeutically equivalent, some patients require dose adjustments to achieve similar trough concentrations [C0] after conversion. Tacrolimus exposure is affected by ethnicity in the de novo setting but the role of ethnicity in determining dose requirements and adjustments after conversion is unknown.
  
  
  METHODS
  In this study, 496 renal transplant recipients (RTRs) were prospectively converted from Tac-BID to Tac-OD, with dose adjustments targeted to achieve similar [C0] at 12 months post-conversion. Renal function, acute rejection and Tac dose adjustments by ethnicity were analyzed.
  
  
  RESULTS
  There were similar numbers of recipients from living and deceased donors. The mean transplant duration was 7 years. Of the RTRs, 60% were Caucasian and 40% were identified as belonging to an ethnic minority. There was no change in estimated renal function (eGFR) post-conversion to Tac-OD. At 12 months, 35/488 (7%) RTRs were receiving a reduced dose, 101/488 (21%) required a dose increase of which 77 (16%) were receiving at least a 30% increase in dose over baseline. The percentage of those in ethnic groups requiring a dose increase of >30% varied from 8.0% for South Asians to 27.5% for East Asians (P = 0.03), despite East Asians having a similar baseline dose of Tac-BID (3.59 mg/day) compared to the entire cohort (3.53 mg/day).
  
  
  CONCLUSIONS
  Ethnicity may play an important role in dosing requirements when converting from Tac-BID to Tac-OD, unrelated to baseline dose. Further investigation is required to determine the reasons for ethnic variability when patients are converted between tacrolimus preparations.
authors.forename: Lauren
authors.initials: L
authors.lastname: Glick
authors.forename: Fernanda
authors.initials: F
authors.lastname: Shamy
authors.forename: Michelle
authors.initials: M
authors.lastname: Nash
authors.forename: Ahmed
authors.initials: A
authors.lastname: Sokwala
authors.forename: Tushar
authors.initials: T
authors.lastname: Malavade
authors.forename: Gv Ramesh
authors.initials: GR
authors.lastname: Prasad
authors.affiliation: Department of Medicine, Division of Nephrology, Keenan Research Institute, St, Michael's, 30 Bond St, Toronto, Ontario M5B1W8, Canada. zaltzmanj@smh.ca.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Zaltzman