CellCept/Iron Study: The Iron Ion-Mycophenolate Mofetil Chelation Complex Interaction in Renal Allograft Recipients

Following oral administration, MMF is rapidly absorbed and is presystemically hydrolyzed to its active form MPA in the liver. It is then metabolized by glucuronyl transferase to its inactive metabolite mycophenolic acid glucuronide (MPAG). MPA and MPAG also undergo a significant enterohepatic recirculation process, which is thought to contribute to the secondary peaks in the serum concentrations.

Pharmacokinetic studies in healthy volunteers have demonstrated the bioavailability to be ~94%. Previous studies have shown that many concomitantly administered medications including magnesium and aluminum containing antacids and cholestyramine, significantly impair bioavailability and decrease serum MPA AUCs from 37% and 40%, respectively.

However, of the potentially significant drug interactions involving MMF, iron may have the most clinically significant consequences. A large portion of the transplant population, particularly renal allograft recipients, experience anemia requiring iron supplementation. A single dose pharmacokinetic study conducted in seven healthy volunteers evaluated the effect of concomitant iron (delayed release preparation) administration on the absorption of MMF. This study reported a significant (89.7%) decrease in AUC among patients receiving concomitant iron and MMF. Although this study provides valuable information, it fails to address several clinically pertinent questions for transplant clinicians including:

1. the potential impact on steady state MPA kinetics in transplant patients,
2. effect of immediate release iron preparation compared with sustained release iron product, and
3. the effect of timing of the dose relative to administration of MMF.