Background
Mycophenolate mofetil (MMF), a prodrug converted to the active form, mycophenolic acid (MPA), is an immunosuppressant used to prevent organ rejection in those with solid organ transplants.   MPA exposure, defined by area-under-the-time curve (AUC) can be estimated using limited sampling strategies (LSS).  However, the relationship between MPA AUC and clinical outcomes has not been studied in pediatrics.  Trough concentrations and single MPA concentration-time points are more practical assessment methods, but do not correlate well with AUC.  The objectives of this study were to describe the relationship between MPA AUC estimated via LSS in pediatric kidney transplant recipients, adverse effects and rates of rejection and to compare clinical outcomes between different MPA monitoring practices.
Methods
Descriptive statistics were used to summarize demographics, adverse effects and rejection.  
Results
Thirty-three kidney transplant patients (91 trough concentrations and 12 LSS sets) aged 2–20 years old who had at least one interpretable MPA plasma concentration were included. The estimated median MPA AUCs (David-Neto and Filler) were higher for those who did not have any adverse effects reported (65.85 and 85.05 mg*h/L, respectively) compared to those who had an adverse effect (60.75 and 54.2 mg*h/L, respectively).  The median trough concentration when no adverse effects occurred was comparable to those with adverse effects.
The median MPA AUC estimated by David-Neto and Filler in which rejection was determined by biopsy was 63.5 mg*h/L (IQR: 59.7-98.7) and 63 mg*h/L (IQR: 58.6-72.8), and in those without rejection, 80.5 mg*h/L (IQR: 74.9-86.1) and 77.05 mg*h/L (IQR: 73.6-80.5), respectively. Of those patients with trough concentration therapeutic drug monitoring, the median trough concentration at which rejection was seen was 3.1 mg/L (IQR: 1.65-4.4), compared to 1.9 mg/L (IQR: 1.4-3.05) for those without rejection.
Conclusions
Neither MPA AUC estimated by LSS nor MPA trough concentration appeared to be associated with occurrence of adverse effects or rejection.

Relationship of limited sampling strategy and adverse effects of mycophenolate mofetil in pediatric renal transplant patients (RELATE)