Safety of the reduced fixed dose of mycophenolate mofetil confirmed via therapeutic drug monitoring in de novo kidney transplant recipients

Background: Mycophenolate mofetil (MMF) is usually prescribed with a reduced fixed dose in Asian kidney transplant recipients (KTRs). However, the clinical efficacy and safety of the fixed dose have not yet been investigated via therapeutic drug monitoring. We evaluated whether reduced fixed-dose MMF is an optimal dosing strategy to achieve the therapeutic target of mycophenolic acid (MPA) exposure in Korean KTRs. Methods: This open-label, prospective study enrolled 50 de novo KTRs prescribed with tacrolimus, corticosteroid, and fixed-dose MMF (1.0–1.5 g/day). The trough level (C₀) and area under the curve (AUC_{0–12 hr}) of MPA were measured at 1 and 24 weeks after kidney transplantation (KT). The relationship of body weight (BW)-adjusted MMF dose with MPA C₀ and MPA AUC_{0–12 hr} was assessed using linear regression analysis. Results: The initial fixed dose of MMF of 1.44 ± 0.16 g/day was adjusted in 24 patients (48.0%) and then reduced to a mean dose of 1.19 ± 0.31 g/day at 24 weeks after KT. Most patients (≥84.0%) attained the minimum required MPA C₀ of 1.0 μg/mL and MPA AUC_{0–12 hr} of 30 μg × hr/mL at 1 and 24 weeks. The BW-adjusted MMF dose demonstrated significant positive correlations with MPA C₀ and MPA AUC_{0– 12 hr} at 1 and 24 weeks after KT. Moreover, 14 patients (28.0%) reported MPA-related adverse events that were pre-dictable based on MPA AUC_{0–12 hr} (cutoff level, 46.4 μg × hr/mL). Conclusion: The current reduced fixed-dose MMF strategy can help achieve the therapeutic target of MPA exposure in tacrolim-us-treated Korean KTRs during the early posttransplant period.