[Pharmacology of mycophenolate mofetil: recent data and clinical consequences]

Nephrologie. 2001;22(7):331-7.
[Article in French]

Abstract

New insights have been recently obtained about pharmacokinetic and pharmacodynamic characteristics of mycophénolate mofetil (MMF). One of the already described MPA metabolite, the acylglucuronide of MPA may 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 renal failure are now available. After renal transplantation, MPA levels vary between immediate post-transplant period, at three months and at two years. The target enzyme is inosine monophosphate dehydrogenase (IMPDH). The genes of the two IMPDH isoforms have been cloned. The bicyclic ring system of MPA packs underneath the hypoxanthine ring of IMPDH, thereby trapping this covalent intermediate of the enzymatic reaction. After renal transplantation, a randomized trial has shown that clinical efficacy is correlated with MPA AUC but side effects are correlated with MMF dosage. When associated with cyclosporine, there is a significant decrease of MPA level. Better knowledge of MMF metabolism, of variability factors and target levels to reach in clinical practice should allow a better use of MMF.

Publication types

  • Review

MeSH terms

  • Animals
  • Biological Availability
  • Biotransformation
  • Cattle
  • Drug Evaluation, Preclinical
  • Drug Interactions
  • Enzyme Inhibitors / adverse effects
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Enzyme Inhibitors / therapeutic use
  • Glucuronosyltransferase / metabolism
  • Graft vs Host Disease / chemically induced
  • Humans
  • IMP Dehydrogenase / antagonists & inhibitors
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / chemistry
  • Immunosuppressive Agents / pharmacology*
  • Immunosuppressive Agents / therapeutic use
  • Isoenzymes / metabolism
  • Kidney / metabolism
  • Kidney Failure, Chronic / metabolism
  • Kidney Failure, Chronic / surgery
  • Kidney Failure, Chronic / therapy
  • Kidney Transplantation
  • Multicenter Studies as Topic
  • Mycophenolic Acid / adverse effects
  • Mycophenolic Acid / analogs & derivatives*
  • Mycophenolic Acid / chemistry
  • Mycophenolic Acid / pharmacology*
  • Mycophenolic Acid / therapeutic use
  • Nucleic Acids / biosynthesis
  • Rabbits
  • Randomized Controlled Trials as Topic
  • Renal Dialysis

Substances

  • Enzyme Inhibitors
  • Immunosuppressive Agents
  • Isoenzymes
  • Nucleic Acids
  • IMP Dehydrogenase
  • Glucuronosyltransferase
  • Mycophenolic Acid