Does the evidence support the use of mycophenolate mofetil therapeutic drug monitoring in clinical practice? A systematic review.
BACKGROUND
The use of mycophenolate mofetil (MMF) as a primary immunosuppressant after transplantation is increasing. A number of factors interact to result in variability in blood levels of mycophenolic acid (MPA) increasing the risk of toxicity. This has led to interest in the application of therapeutic drug monitoring to optimize its use.


METHODS
A systematic literature search was performed using Medline, Embase, the Cochrane Central Registry of Clinical Trials, the Transplant Library, and clinical trial registries for studies investigating the clinical role of MMF pharmacokinetic drug monitoring. Studies relating monitoring regimens to clinical outcomes were included.


RESULTS
The majority of studies are retrospective in nature, demonstrating good correlation between the full total MPA area-under-the-curve and the risk of acute rejection, but not toxicity. Free MPA levels may better predict toxicity. Single-point parameters, in particular trough levels, show poor correlation with the risk of acute rejection and toxicity, and in prospective studies do not improve clinical outcomes. Limited sampling strategies using samples from the first few hours postdose allow good prediction of the full area-under-the-curve, and monitoring using these strategies may improve clinical outcomes.


CONCLUSIONS
The current data regarding therapeutic monitoring of MMF is of limited quality. The most promising results to date come from limited sampling strategies, with benefit seen in one prospective randomized trial. Further prospective trials and longer follow-up are required to investigate the optimum sampling strategy and subsets of patients who may benefit from monitoring, but the current evidence in favor of monitoring is weak.
Knight
Simon R
SR
Morris
Peter J
PJ
D019540:Area Under Curve; D016903:Drug Monitoring / Q000639:trends*; D006084:Graft Rejection / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010818:Practice Patterns, Physicians'; D014181:Transplantation Immunology
D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid