Pharmacokinetics of Mycophenolic Acid and Dose Optimization in Children After Intestinal Transplantation.

BACKGROUND: Mycophenolate mofetil (MMF) or enteric-coated mycophenolate sodium (MPS) is now commonly used in pediatric intestinal transplantation (Tx), but to date, no clear recommendations regarding the dosing regimen have been made in this population. The aim of this study was to determine the MMF/MPS dosage required to achieve an area under the plasma concentration-time curve from 0 to 12 hours (AUC0-12) for mycophenolic acid (MPA) greater than 30 mg·h·L in children after intestinal transplantation.

METHODS: A pharmacokinetic study was conducted in 8 children (median, 9.4 years; range, 0.75-15.8 years) at a median time of 113 months (range, 1.5-160 months) after intestinal transplantation.

RESULTS: MMF was initially introduced at a low median starting dose of 687 mg·m·d (range, 310-1414 mg·m·d). One of the 3 patients who received MPS and 2 of the 6 patients who received MMF had an MPA AUC0-12 value below 30 mg.h.L. The median MMF dosage had to be increased by 91% (1319 mg·m·d versus 687 mg·m·d) to reach AUC0-12 values above the defined target level of 30 mg·h·L.

CONCLUSIONS: When used in combination with tacrolimus and steroids, an initial MMF dose of 600 mg/m twice a day would be recommended to children after intestinal transplantation to achieve MPA exposure similar to those observed in adults and children after the transplantation of other organs. Further studies are required to recommend a suitable dosage for pediatric intestinal transplant recipients who receive MPA.