Tacrolimus (Prograf, Astellas Pharma Europe Ltd, Staines, UK; referred to as Tacrolimus BID), an established immunosuppressant for the prevention and treatment of allograft rejection in kidney, liver and heart transplantation, is administered twice daily (BID). A prolongedrelease tacrolimus formulation (Advagraf, Astellas Pharma Europe Ltd, Staines, UK; referred to as Tacrolimus QD) allows once-daily dosing, with the potential for improving treatment adherence. Nonadherence is a major cause of preventable graft loss (1–3). Interventions that improve treatment adherence, such as morning dosing and reducing administration frequency (4,5), may also improve longterm outcomes (6–8).
Both tacrolimus formulations have demonstrated comparable steady-state systemic tacrolimus exposure in stable and de novo kidney and liver transplant patients. Importantly, the relationship between trough levels and systemic exposure was identical (9), and thus enabled monitoring by trough levels as a surrogate for area under the curve as used with Tacrolimus BID. This study was performed to yield further results comparing Tacrolimus BID and QD formulations in a double-blind fashion in combination with low-dose mycophenolate mofetil (MMF) and corticosteroids without antibody induction.