Pharmacodynamic monitoring of the conversion from mycophenolate mofetil to enteric-coated mycophenolate sodium in stable kidney-allograft recipients

Int Immunopharmacol. 2008 May;8(5):769-73. doi: 10.1016/j.intimp.2008.01.023. Epub 2008 Feb 20.

Abstract

Background: The formulations of mycophenolic acid, i.e., mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), seem to have different pharmacokinetic profiles. The aim of this study was to compare the effects MMF and EC-MPS on T-cell proliferation, T-cell activation, T-cell function, and lymphocyte subsets. CLINICAL STUDY AND METHODS: Ten stable kidney-transplant patients on standard maintenance therapy of tacrolimus and MMF (1 g/d), with or without steroids, were converted from MMF to EC-MPS at equivalent dose (720 mg/d). Tacrolimus and steroid doses remained unchanged before, and at 1, 2, 3, and 6 months (M) after conversion. Intra T-lymphocyte cytokines IL-2 and TNF-alpha, lymphocyte-activation surface markers (CD25 and CD71), T-cell proliferation (PCNA+ PI(high)), total lymphocyte count, as well as lymphocytes subsets (CD2, CD3, CD4, CD8, CD19, NK cells) were measured by flow cytometry before conversion and at M1, M2, M3, and M6.

Results: We found no significant differences of MMF versus EC-MPS on lymphocyte function. T-cell proliferation and T-cell activation (CD25 and CD71 expression), but not cytokine expression (TNF-alpha and IL-2), showed a trend to increase after conversion from MMF to EC-MPS. Total lymphocyte, CD2, CD3, CD4, CD8, and NK cells counts were not significantly modified.

Conclusion: This study revealed a trend to a lower immunosuppression with EC-MPS as compared to MMF in stable renal transplant patients.

Publication types

  • Clinical Trial
  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Proliferation / drug effects
  • Chemistry, Pharmaceutical
  • Cytokines / biosynthesis
  • Drug Monitoring
  • Flow Cytometry
  • Humans
  • Immunosuppressive Agents / administration & dosage
  • Immunosuppressive Agents / blood*
  • Immunosuppressive Agents / pharmacokinetics
  • Kidney Transplantation / immunology*
  • Lymphocyte Count
  • Lymphocyte Subsets / drug effects
  • Lymphocyte Subsets / immunology
  • Male
  • Middle Aged
  • Mycophenolic Acid / administration & dosage
  • Mycophenolic Acid / analogs & derivatives*
  • Mycophenolic Acid / blood
  • Mycophenolic Acid / pharmacokinetics
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Tablets, Enteric-Coated
  • Tacrolimus / administration & dosage
  • Tacrolimus / pharmacology

Substances

  • Cytokines
  • Immunosuppressive Agents
  • Tablets, Enteric-Coated
  • Mycophenolic Acid
  • Tacrolimus