Population Pharmacokinetics of Mycophenolic Acid: An Update

Abstract

The most recent comprehensive reviews on the population pharmacokinetics of mycophenolic acid (MPA) were published in 2014. Since then, several population pharmacokinetic studies on MPA have been published. The majority of literature is still focused on the kidney transplant population, although studies have also been conducted in liver and lung transplantation, autoimmune diseases, and hematopoietic stem cell transplant. While the majority of the model building is still based on parametric non-linear mixed-effects modeling, recent studies suggest the suitability of other methodologies. Additionally, instead of just focusing on pharmacokinetic modeling, a trend toward describing the relationships between pharmacokinetic and pharmacodynamic parameters is observed. Given the importance of enterohepatic recirculation (EHR) in the pharmacokinetics of MPA, more authors have attempted to characterize this process in their models. Overall, the recent models have become more sophisticated and incorporate EHR, pharmacodynamic relationships, and metabolites while maintaining many of the population values and covariates identified previously. However, the number of MPA population pharmacokinetic models describing the enteric-coated formulation of MPA (EC-MPA) is still limited. Given the increasing use of EC-MPA, more studies are needed to fill this literature gap. In addition, few studies are yet available characterizing free MPA concentration or MPA metabolites. Given the extensive protein binding, low to intermediate extraction, and intrinsic clearance characteristics of MPA in humans, including these variables would improve the population structural models.