title: Large scale analysis of routine dose adjustments of mycophenolate mofetil based on global exposure in renal transplant patients.
abstract: BACKGROUND
  We report a feasibility study based on our large-scale experience with mycophenolate mofetil dose adjustment based on mycophenolic acid interdose area under the curve (AUC) in renal transplant patients.
  
  
  METHODS
  Between 2005 and 2010, 13,930 requests for 7090 different patients (outside any clinical trial) were posted by more than 30 different transplantation centers on a free, secure web site for mycophenolate mofetil dose recommendations using three plasma concentrations and Bayesian estimation.
  
  
  RESULTS
  This retrospective study showed that 1) according to a consensually recommended 30- to 60-mg·h/L target, dose adjustment was needed for approximately 35% of the patients, 25% being underexposed with the highest proportion observed in the first weeks after transplantation; 2) when dose adjustment had been previously proposed, the subsequent AUC was significantly more often in the recommended range if the dose was applied than not at all posttransplantation periods (72-80% vs. 43-54%); and 3) the interindividual AUC variability in the "respected-dose" group was systematically lower than that in the "not respected-dose" group (depending on the posttransplantation periods; coefficient of variation %, 31-41% vs 49-70%, respectively). Further analysis suggested that mycophenolic acid AUC should best be monitored at least every 2 weeks during the first month, every 1 to 3 months between months 1 and 12, whereas in the stable phase, the odds to be still in the 30- to 60-mg·h/L range on the following visit was still 75% up to 1 year after the previous dose adjustment.
  
  
  CONCLUSIONS
  This study showed that the monitoring of mycophenolate mofetil on the basis of AUC measurements is a clinically feasible approach, apparently acceptable by the patients, the nurses, and the physicians owing to its large use in routine clinics.
authors.affiliation: CHU Limoges, Service de Pharmacologie et Toxicologie, Limoges, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Saint-Marcoux
authors.forename: Soizic
authors.initials: S
authors.lastname: Vandierdonck
authors.forename: Aurélie
authors.initials: A
authors.lastname: Prémaud
authors.forename: Jean
authors.initials: J
authors.lastname: Debord
authors.forename: Annick
authors.initials: A
authors.lastname: Rousseau
authors.forename: Pierre
authors.initials: P
authors.lastname: Marquet
mesh_terms: D019540:Area Under Curve; D001499:Bayes Theorem; D054796:Drug Dosage Calculations; D016903:Drug Monitoring / Q000379:methods*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D016030:Kidney Transplantation; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D012189:Retrospective Studies
chemical_list: D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid