Area Under the Curve-Guided Therapeutic Drug Monitoring of Mycophenolic Acid in Lung Transplant Recipients: Volumetric Absorptive Microsampling and Population Pharmacokinetic-Based Limited Sampling Strategies

Mycophenolate mofetil (MMF), a prodrug rapidly converted to mycophenolic acid (MPA), is widely used after lung transplantation, but fixed-dose therapy is complicated by exposure variability, enterohepatic recirculation, drug interactions, and limited routine use of area under the concentration-time curve (AUC)-guided therapeutic drug monitoring (TDM). Volumetric absorptive microsampling (VAMS) may support less invasive sampling, including later sampling windows relevant to enterohepatic recirculation. This prospective exploratory cohort study enrolled Taiwanese lung transplant recipients receiving MMF for more than three days. MPA concentrations were collected using VAMS at eight time points over a 12-hour dosing interval. Full-profile AUC 0–12 was calculated, multiple linear regression was used to develop limited sampling strategies (LSS), and agreement between LSS-predicted and reference AUC values was assessed using Bland-Altman analysis. Exploratory population pharmacokinetic (popPK) modeling was used to characterize exposure variability. Nine patients were enrolled. MPA exposure was highly variable and generally below the commonly cited AUC 0–12 target range of 30–60 mg·h/L (median AUC 0–12 : 18.11 mg·h/L; IQR: 14.33). Two- and three-point LSS models demonstrated strong predictive performance, particularly strategies incorporating both early absorption and later enterohepatic recirculation windows (C1 and C8). Leukopenia and infectious complications were common despite low total MPA exposure. Exploratory popPK analysis supported a one-compartment model with dual absorption pathways and identified patient-related factors associated with exposure variability. VAMS-based LSS may provide a practical approach for estimating MPA AUC 0–12 in Taiwanese lung transplant recipients. These findings support simplified AUC-guided MMF TDM, while the exploratory popPK findings require validation in larger cohorts.