A limited sampling model to estimate the area under the curve of mycophenolic acid in hematopoietic stem cell transplantation recipients.

Abstract

Relationship between the areas under the curve (AUC) of mycophenolic acid (MPA) and the likelihood of rejection is well-established in solid organ transplantation recipients. In hematopoietic stem cell transplantation (HSCT), MPA AUC is also linked to graft versus host disease. This study aimed to develop a simplified method to estimate MPA AUC_0-12 in Chinese patients undergoing allogeneic HSCT (allo-HSCT). Intensive sampling was conducted in 22 patients who were orally administered mycophenolate mofetil. Plasma concentrations of total MPA were measured, and a model predicting AUC_0-12 using data from these 22 patients was constructed through regression analysis. The accuracy of the most suitable model was assessed in an additional 20 patients. None of the individual MPA concentrations showed a strong correlation with AUC_0-12 (r² < 0.7). Models utilizing 4 or more concentrations were found to effectively estimate MPA AUC_0-12 (r² > 0.87). The most operationally feasible model demonstrated good predictive performance with a mean absolute percentage error (APE%) < 20%. Single MPA concentrations showed poor correlation with MPA AUC_0-12. A model utilizing 4 oral concentrations (0, 0.5, 1, and 4 h postdose) over a 12-h period could effectively estimate MPA AUC_0-12 with precise results and minimal bias.