Pharmacokinetics-based optimal dose-exploration of mycophenolate mofetil in allogeneic hematopoietic stem cell transplantation

Int J Hematol. 2008 Jul;88(1):104-110. doi: 10.1007/s12185-008-0093-4. Epub 2008 May 14.

Abstract

For better clinical outcomes of mycophenolate mofetil (MMF) in allogeneic hematopoietic stem cell transplantation (alloSCT), higher mycophenolic acid (MPA) plasma levels are proposed to be desirable. Here, we investigate the optimal MMF dosing strategy based on pharmacokinetic studies in 20 Japanese alloSCT patients. The first 11 patients received MMF twice daily at an escalated dose from 15 mg/kg, according to real-time pharmacokinetic monitoring of the total MPA area under the curve (AUC). In the subsequent nine patients, MMF was given at a fixed dose of 1,000 mg three-times daily. The pharmacokinetic data revealed that the dose escalation in each individual did not always increase the AUC. In contrast, the increase of dosing frequency could statistically keep higher MPA plasma levels, as reflected in higher concentration at steady state (C (ss)) or trough value (C (trough)). There was no symptomatic adverse event in both groups. These results suggest that MMF administration of every 8 h after alloSCT would be better to maintain higher MPA plasma levels than that of every 12 h even in the same daily dose. Further studies are necessary to confirm the clinical benefit of MMF to prevent graft failure, as well as severe aGVHD.

Publication types

  • Case Reports
  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adult
  • Aged
  • Asian People
  • Female
  • Graft Rejection / prevention & control*
  • Graft vs Host Disease / prevention & control*
  • Hematologic Neoplasms / therapy*
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Immunosuppressive Agents / administration & dosage
  • Immunosuppressive Agents / pharmacokinetics*
  • Male
  • Middle Aged
  • Mycophenolic Acid / administration & dosage
  • Mycophenolic Acid / analogs & derivatives*
  • Mycophenolic Acid / pharmacokinetics
  • Peripheral Blood Stem Cell Transplantation*
  • Transplantation, Homologous

Substances

  • Immunosuppressive Agents
  • Mycophenolic Acid