Pharmacology of mycophenolate mofetil: recent insights and clinical consequences

New insights have been recently obtained about pharmacokinetic and pharmaco dynamic characteristics of mycophenolate mofetil (MMF). One of the already described MPA metabolite, the acyl-glucuronide of MPA ma y be both active and responsible for some side-effects. Glucuronidation is mediated by at least two uridine diphosphate glucuronosyltransferase (UGT) forms, namely UGT1A8 and UGT1A10 whose variability could explain the inter- and intra-individual variability of MMF metabolism. MPA pharmacokinetic data in dialyzed patients or in patients with chronic r enal failure are now available. After renal transplantation, MPA levels var y between immediate post-transplant period, at three months and at two year s. The target enzyme is inosine monophosphate deshydrogenase (IMPDH). The gene s of the two IMPDH isoforms have been cloned. The bicyclic ring system of M PA packs underneath the hypoxanthine ring of IMPDH, thereby trapping this c ovalent intermediate of the enzymatic reaction. After renal transplantation, a randomized trial has shown that clinical eff icacy is correlated with MPA AUC but side effects are correlated with MMF d osage. When associated with ciclosporine, there is a significant decrease o f MPA level. Better knowledge of MMF metabolism, of variability factors and target level s to reach in clinical practice should allow a better use of MMF.