Model-informed AUC-guided monitoring of enteric-coated mycophenolate sodium: population pharmacokinetics and clinical transferability

Delayed, variable absorption and enterohepatic recirculation complicate estimation of mycophenolic acid (MPA) exposure after enteric-coated mycophenolate sodium (EC-MPS) administration. This narrative review examines nine population pharmacokinetic development studies and related limited-sampling and clinical evidence to assess procedures for estimating total plasma MPA area under the concentration–time curve over 12 h (AUC 0–12h ). Selected three- or four-sample regression and Bayesian procedures support AUC estimation, mainly in adult kidney transplant recipients. Validation against densely sampled noncompartmental AUC assesses agreement with a sampling-based reference; comparison with full-profile AUC from the same model assesses recovery of model-derived exposure from fewer samples. Patient holdout alone does not ensure independent validation of sampling schedules, and sparse low-exposure data limit assessment of underexposure detection. The commonly used 30–60 mg h/L target is supported mainly by mycophenolate mofetil studies in kidney transplantation and requires assay- and indication-specific interpretation. Direct EC-MPS studies support exposure–outcome associations and the feasibility of concentration-guided dosing, while evidence of improved clinical outcomes remains limited. These findings guide selection of candidate monitoring procedures by matching the estimator, sampling schedule, assay and exposure target to the intended population and dosing decision.