Dose optimization of mycophenolate mofetil when administered with a low dose of tacrolimus in cadaveric renal transplant recipients

Transplantation. 2001 Jul 15;72(1):63-9. doi: 10.1097/00007890-200107150-00014.


Background: Supplementation of immunosuppressive therapy with mycophenolate mofetil (MMF) has been found to reduce the rate of acute rejection in renal transplantation. We report a dose-finding study for MMF when administered in combination with low-dose tacrolimus and corticosteroid prophylaxis in cadaveric renal transplant recipients.

Methods: Two hundred thirty-two patients at 16 centers were enrolled in this randomized, parallel-group study. The three treatment groups were tacrolimus and corticosteroids (MMF-0 group, n=82); tacrolimus, corticosteroids, and 1 g of MMF daily (MMF-1 g group, n=79); and tacrolimus, corticosteroids, and 2 g of MMF daily (MMF-2 g group, n=71). Study duration was 6 months, and patients were followed up for patient and graft survival for 12 months.

Results: At 6 months posttransplantation, daily doses of 1 g and 2 g of MMF were associated with significantly lower rates of acute rejection compared with tacrolimus alone. The Kaplan-Meier rates were 48.5%, 24.9%, and 22.9%, respectively, for the three treatment groups when acute rejection was determined by clinical criteria (P=0.007). At month 12, patient survival rates were 100%, 97.5%, and 97.2% and graft survival rates were 90.2%, 92.4%, and 93.0% for the MMF-0 group, MMF-1 g group, and the MMF-2 g group, respectively. Gastrointestinal adverse events and leukopenia were higher in the MMF groups, especially in the MMF-2 g group (P<0.05).

Conclusions: Low-dose tacrolimus combined with a MMF dose of 1 g daily and corticosteroids provided an optimized efficacy and safety profile. A higher dose of MMF (2 g) was associated with greater toxicity without a significant improvement in efficacy.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Cortex Hormones / administration & dosage
  • Adrenal Cortex Hormones / adverse effects
  • Adrenal Cortex Hormones / therapeutic use
  • Adult
  • Cadaver
  • Dose-Response Relationship, Drug
  • Drug Therapy, Combination
  • Female
  • Gastrointestinal Diseases / chemically induced
  • Graft Rejection / prevention & control
  • Graft Survival / drug effects
  • Humans
  • Immunosuppressive Agents / administration & dosage*
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / therapeutic use
  • Kidney Transplantation*
  • Leukopenia / chemically induced
  • Male
  • Middle Aged
  • Mycophenolic Acid / administration & dosage*
  • Mycophenolic Acid / adverse effects
  • Mycophenolic Acid / analogs & derivatives
  • Mycophenolic Acid / therapeutic use
  • Survival Analysis
  • Tacrolimus / administration & dosage*
  • Tacrolimus / adverse effects
  • Tacrolimus / therapeutic use
  • Time Factors
  • Treatment Outcome


  • Adrenal Cortex Hormones
  • Immunosuppressive Agents
  • Mycophenolic Acid
  • Tacrolimus