Similar MPA exposure on modified release and regular tacrolimus

Area of Science:

• Nephrology
• Pharmacology
• Transplantation

Background:

• Concomitant immunosuppression can influence mycophenolate mofetil exposure.
• Astellas developed a once-daily modified-release tacrolimus (TacMR) formulation to potentially improve adherence.
• The effect of TacMR on mycophenolic acid (MPA) area under the concentration-time curve (AUC) is unknown.

Purpose of the Study:

• To investigate whether MPA AUC differs between standard twice-daily tacrolimus (Tac) and once-daily modified-release tacrolimus (TacMR).

Main Methods:

• A 2-by-2 crossover study involving 20 stable renal transplant recipients.
• Patients either continued their usual Tac or switched to TacMR for 12 weeks, then crossed over.
• Pharmacokinetic profiles were assessed using limited sampling, and MPA AUC was calculated.

Main Results:

• MPA AUC values were 42.24 (16.98) mg·h·L(-1) on baseline Tac, 37.18 (13.75) mg·h·L(-1) on TacMR, and 40.09 (16.69) mg·h·L(-1) when switched back to Tac.
• No statistically significant differences in MPA AUC were observed between the Tac formulations (P = 0.1327).

Conclusions:

• Converting renal transplant recipients from standard tacrolimus to modified-release tacrolimus does not alter mycophenolic acid pharmacokinetics.
• TacMR is a viable alternative for patients requiring tacrolimus therapy, potentially improving adherence without compromising MPA exposure.