Therapeutic drug monitoring of mycophenolic acid in renal transplant recipients

Transplant Proc. 2005 Mar;37(2):859-60. doi: 10.1016/j.transproceed.2004.12.238.

Abstract

Immunosuppressive regimens including mycophenolate mofetil (MMF, Cellcept) were used in a renal transplant transplant program since May 2000 including 67 patients in whom it was the primary drug. Acute rejection (AR) occurred in 9 cases (13%) with 1-year graft survival rate of 96.8%. Pharmacokinetic (PK) studies of mycophenolic acid (MPA) were performed in 46 recent patients (total, 127 times). There was no correlation between dose (mg/kg) and blood concentration (AUC0-9: r2= 0.27). AUC0-9 was well correlated with AUC0-4 (r2= 0.91), but not with a single timepoint concentration. MPA AUC0-9 level was significantly higher among the AR-negative group (n = 33; 34.2 +/- 16.8 ng.hr/mL) compared with AR-positive group (n = 3; 28.2 +/- 1.9 ng.hr/mL; P = .04085) over the 2 weeks after transplantation. MPA AUC0-9 level was higher among the adverse event (AE-positive) group (n = 15; 39.2 +/- 22.8 ng.hr/mL) compared with the negative group (n = 21; 30.1 +/- 8.0 ng.hr/mL; P = .08772) within 2 weeks after transplantation. These results suggest the necessity of measuring AUC for therapeutic drug monitoring (TDM) of MMF-containing immunosuppressive therapy. The possible target level of MPA AUC0-9 would be approximately 30 ng.hr/mL using the present immunosuppressive regimen.

Publication types

  • Clinical Trial
  • Comparative Study

MeSH terms

  • Adolescent
  • Adult
  • Cadaver
  • Child
  • Cyclosporine / therapeutic use
  • Drug Monitoring / methods
  • Graft Rejection / epidemiology
  • Humans
  • Immunosuppressive Agents / blood
  • Immunosuppressive Agents / pharmacokinetics*
  • Immunosuppressive Agents / therapeutic use
  • Kidney Transplantation / immunology*
  • Kidney Transplantation / mortality
  • Living Donors
  • Middle Aged
  • Mycophenolic Acid / blood
  • Mycophenolic Acid / pharmacokinetics*
  • Mycophenolic Acid / therapeutic use
  • Survival Analysis
  • Tissue Donors

Substances

  • Immunosuppressive Agents
  • Cyclosporine
  • Mycophenolic Acid