title: The impact of routine mycophenolate mofetil drug monitoring on the treatment of cardiac allograft rejection.
abstract: BACKGROUND
  Mycophenolate mofetil (MMF) is a unique immunosupressive agent that has been shown to be efficacious in the treatment of cardiac allograft rejection. The utility of therapeutic drug monitoring on rejection prophylaxis and treatment is inconclusive. This study was undertaken to evaluate the incidence of rejection in relation to MMF trough level following heart transplantation.
  
  
  METHODS
  Between May 1998 and February 1999, we retrospectively analyzed the clinical outcome of 215 heart transplant patients who had routine monitoring of MMF trough level at the time of scheduled endomyocardial biopsy. Patients were divided into three groups according to the time interval post transplant, and were evaluated in relation to the MMF trough level. Group I, 104 patients within 6 months of transplant; Group II, 90 patients, 6-12 months post transplant; and Group III, 71 patients beyond one year of transplant. Fifty patients had samples in more than one group. Rejection was defined as Grade > or = 3A based on ISHLT criteria. Mean follow-up period was 179+/-52 days.
  
  
  RESULTS
  A significantly decreased incidence of rejection was noted in the samples with MMF trough level > or = mg/l compared to those with less than 2 mg/l inpatients evaluated within the first year of transplant (Group I: 8.8% vs. 14.9%, Group II: 4.2% vs. 11.3%, both P=0.05). In the presence of therapeutic cyclosporine (CSA) or tacrolimus (FK) blood levels, the incidence of rejection decreased significantly when MMF trough level was > or = 2 mg/l compared to samples with MMF trough level <2 mg/l (3.6% vs. 14.4%, P=0.005). No significant difference was noted in the presence of subtherapeutic CSA or FK levels (15.4% vs. 13.9%, P=NS).
  
  
  CONCLUSIONS
  Monitoring of MMF trough levels may play a role in the management of cardiac transplant recipients during the first year post transplant.
authors.affiliation: Department of Cardiology and Cardiothoracic Surgery, Kaufman Center for Heart Failure, Cleveland Clinic Foundation, OH 44195, USA.
authors.forename: M H
authors.initials: MH
authors.lastname: Yamani
authors.forename: R C
authors.initials: RC
authors.lastname: Starling
authors.forename: M
authors.initials: M
authors.lastname: Goormastic
authors.forename: F
authors.initials: F
authors.lastname: Van Lente
authors.forename: N
authors.initials: N
authors.lastname: Smedira
authors.forename: P
authors.initials: P
authors.lastname: McCarthy
authors.forename: J B
authors.initials: JB
authors.lastname: Young
mesh_terms: D000328:Adult; D016572:Cyclosporine / Q000097:blood / Q000627:therapeutic use; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D005260:Female; D006084:Graft Rejection / Q000188:drug therapy* / Q000453:epidemiology; D016027:Heart Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood* / Q000627:therapeutic use*; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000097:blood / Q000627:therapeutic use; D016559:Tacrolimus / Q000097:blood / Q000627:therapeutic use; D014184:Transplantation, Homologous
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D009173:Mycophenolic Acid; D016559:Tacrolimus