Therapeutic drug monitoring of mycophenolate mofetil in pediatric patients: novel techniques and current opinion

ABSTRACT

Introduction: Mycophenolate mofetil (MMF) is an ester prodrug of the immunosuppressant mycophenolic acid (MPA) and is recommended and widely used for maintenance immunosuppressive therapy in solid organ and stem-cell transplantation as well as in immunological kidney diseases. MPA is a potent, reversible, noncompetitive inhibitor of the inosine monophosphate dehydrogenase (IMPDH), a crucial enzyme in the de novo purine synthesis in T- and B-lymphocytes, thereby inhibiting cell-mediated immunity and antibody formation. The use of therapeutic drug monitoring (TDM) of MMF is still controversial as outcome data of clinical trials are equivocal.

Areas covered: This review covers in great depth the existing literature on TDM of MMF in the field of pediatric (kidney) transplantation. In addition, the relevance of TDM in immunological kidney diseases, in particular childhood nephrotic syndrome is highlighted.

Expert opinion: TDM of MMF has the potential to optimize therapy in pediatric transplantation as well as in nephrotic syndrome. Limited sampling strategies to estimate MPA exposure increase its feasibility. Future perspectives rather encompass approaches reflecting total immunosuppressive load than single drug TDM.

KEYWORDS:

• IMPDH
• limited sampling strategies
• mycophenolic acid
• pediatric transplantation
• pharmacodynamics
• pharmacogenetics
• pharmacokinetic
• trough level

Article highlights

1. Distinct pharmacokinetics of mycophenolic acid in the pediatric cohort

2. Value of therapeutic drug monitoring of mycophenolic acid

3. Pharmacodynamic and pharmacogenetic approach

4. Monitoring of immunosuppressive load – future perspective

This box summarizes the key points contained in the article.

Declaration of interest

LT Webber has received travel grants from Astellas Pharma GmbH and research grants from Chiesi GmbH. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This paper was not funded.