Pre-transplant mycophenolate mofetil pharmacokinetics in Mexican children

Mycophenolate mofetil is an immunosuppressive pro-drug frequently used to prevent renal graft rejection. It is hydrolyzed by esterases to obtain the active drug mycophenolic acid (MPA). There is high inter-patient variation in mycophenolic acid pharmacokinetics. Area under the concentration versus time curve (AUC) is used for therapeutic drug monitoring and recommended levels are 30-60 microg x hr/L. The aim of this study was to determine mycophenolic acid pharmacokinetics in children awaiting renal allograft in order to predict mycophenolate mofetil dose requirements. Children with end-stage renal disease on the waiting list for renal allograft transplantation were invited to participate in the study. A nine-point pharmacokinetic profile was performed. All patients received a single dose (600 mg/m2, subcutaneously) of mycophenolate mofetil at time zero. Mycophenolic acid was measured by HPLC. The AUC0-12h was estimated by the trapezoidal rule. Ten children were included in the study. Mean age was 13.5 +/- 3.5 years. The median AUC0-12h was 20.3 microg x hr/L, median Cmax = 0.7 microg/mL. Two children (20%) had no detectable levels of mycophenolic acid after a single mycophenolate mofetil dose, other two patients had AUC > 60 microg x hr/L. One patient had abdominal pain 1 hr after the mycophenolate mofetil dose. Twenty percent of our patients had AUC0-12h higher than the recommended value after a single mycophenolate mofetil dose, those patients should receive lower mycophenolate mofetil dose since the beginning of the transplant to avoid adverse events, and another 20% of patients had no detectable mycophenolic acid levels after a single mycophenolate mofetil dose. UGT1A9 gene polymorphisms remain to be studied in our patients, since they could explain the differences in bioavailability.