Effects of food and antacid on the pharmacokinetics of single doses of mycophenolate mofetil in rheumatoid arthritis patients

1 Mycophenolate mofetil (MMF) is a prodrug of mycophenolic acid (MPA) and is being developed for the prevention of rejection following solid organ transplantation. This crossover study investigated the effect of food and antacid (Maalox^® TC) on the plasma pharmacokinetics of MPA and its inactive glucuronide metabolite MPAG after giving single 2  g MMF doses orally to rheumatoid arthritis patients.
2 With food, the AUC of MPA in plasma was equivalent to that following an overnight fast. MPA t _max was slightly delayed and C _max was lowered about 25%, consistent with delay in gastric emptying in the fed state. MPAG C _max and AUC were higher in the fed relative to the fasting state, suggesting more complex processes involving changes in glucuronidation may also be occurring with food.
3 With antacid, AUC of MPA was lowered about 15% compared with fasting and C _max was decreased 37%. Plasma MPAG parameters were similarly reduced. These parallel changes in MPA and MPAG are consistent with reduced absorption.
4 The changes in MPA with both food and antacid are small in comparison with the interpatient variability and are not likely to have clinically major effects; the changes in MPAG are of mechanistic interest.