Mycophenolate mofetil (MMF) in heart transplantation: rejection prevention and treatment.
Mycophenolate mofetil (MMF), the morpholinoethylester of mycophenolic acid, inhibits the de novo pathway for purine synthesis. Evidence suggests that MMF suppresses lymphocyte function more than that of neutrophils, erythrocytes, and other rapidly dividing cell lines that can utilize salvage pathways for purine synthesis. While rigorous efficacy data await the completion of an ongoing, multicenter, prospectively randomized, placebo-controlled trial, long-term safety data are, however, available from numerous uncontrolled trials in cardiac transplantation. Dose-ranging trials in 49 heart recipients suggest that doses > or = 4000 mg/d are associated with significant, reversible gastrointestinal toxicity when compared with doses < 4000 mg/d (p < 0.001). Patients receiving > or = 1000 mg/d may have fewer rejection episodes. Even in the long term, changing from azathioprine to MMF is associated with increases in hematocrit (p < 0.001), total WBC count (p < 0.005), and absolute neutrophil count (p < 0.005). Successful use of MMF in refractory cardiac allograft rejection suggests an advantage over azathioprine. MMF is safe and appears to be at least as effective as azathioprine for immunosuppression following heart transplantation.
Renlund
D G
DG
Department of Internal Medicine, University of Utah Health Sciences Center, Salt Lake City 84132, USA.
Gopinathan
S K
SK
Kfoury
A G
AG
Taylor
D O
DO
D000818:Animals; D001379:Azathioprine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D006084:Graft Rejection / Q000188:drug therapy / Q000517:prevention & control*; D016027:Heart Transplantation / Q000009:adverse effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology; D015337:Multicenter Studies as Topic; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010919:Placebos; D011446:Prospective Studies; D011687:Purines / Q000037:antagonists & inhibitors; D016032:Randomized Controlled Trials as Topic; D012449:Safety
D007166:Immunosuppressive Agents; D010919:Placebos; D011687:Purines; D009173:Mycophenolic Acid; D001379:Azathioprine; C030985:purine