Tacrolimus prolonged release in kidney transplantation

Area of Science:

• Transplantation Immunology
• Pharmacology

Background:

• Nonadherence to immunosuppressive therapy is a significant barrier to improving long-term post-transplant outcomes.
• Once-daily dosing regimens may enhance patient adherence and potentially improve long-term results.

Purpose of the Study:

• To evaluate the efficacy and safety of tacrolimus prolonged release (Advagraf) compared to tacrolimus immediate release (Prograf).
• To assess the benefits of a once-daily dosing regimen for immunosuppression in transplant recipients.

Main Methods:

• Phase II pharmacokinetic studies for dose conversion and monitoring.
• Phase III multicenter studies to assess long-term efficacy and safety.
• Comparison of Advagraf and Prograf in de novo transplant recipients and those converted from Prograf.

Main Results:

• Advagraf can be converted from Prograf on a one-to-one daily dose basis with similar trough levels.
• De novo Advagraf use shows comparable efficacy and safety to Prograf, requiring therapeutic drug monitoring.
• Phase III studies demonstrate good long-term efficacy and safety, with Advagraf showing potentially lower variability and improved renal function measures.

Conclusions:

• Once-daily Advagraf offers a viable alternative to Prograf, potentially improving patient adherence.
• Advagraf may enhance long-term graft protection and patient outcomes through improved medication adherence and consistent immunosuppression.
• The pharmacokinetic profile and clinical data support Advagraf's role in maintaining adequate immunosuppression post-transplantation.