MPA AUC0-12h under different dosing scenarios.

BackgroundMissed doses of mycophenolate mofetil (MMF) are frequent in transplant recipients and may lead to subtherapeutic exposure to mycophenolic acid (MPA), potentially compromising graft function. However, current guidance on how to manage such deviations remains empirical and is not supported by pharmacokinetic evidence.MethodsWe used two validated population pharmacokinetic models of MPA to simulate steady-state exposure in virtual cohorts of renal transplant recipients treated with MMF. Scenarios included full missed doses, delays in intake (2–10 hours), and compensation strategies (50% or 100% added at the next dose). Simulations were performed for six dose regimens (500–1250 mg BID) and analyzed in terms of AUC0–12h, proportion of patients outside the target range (30–60 mg·h/L), and time to return to steady state.ResultsA fully missed dose resulted in a 40–60% reduction in AUC0–12h, with delayed return to steady state (up to 72 hours). Delays ≤6 hours caused minimal impact (ConclusionsModel-based simulations suggest that a rational response to MMF dose omissions can mitigate underexposure while avoiding toxicity. These strategies may support clinicians in managing missed doses and optimizing immunosuppressive therapy in kidney transplant recipients.