title: Steady-state mycophenolate mofetil pharmacokinetic parameters enable prediction of systemic lupus erythematosus clinical flares: an observational cohort study.
abstract: BACKGROUND
  The aim of this study was to determine whether mycophenolate mofetil (MMF) pharmacokinetics (PK) under combined MMF and prednisone remission-maintenance therapy can predict systemic lupus erythematosus (SLE) clinical flares.
  
  
  METHODS
  At inclusion, steady-state PK parameters of the MMF active form, mycophenolic acid (MPA), and its glucuronide metabolite (MPAG) were determined for 25 stable SLE patients without renal manifestations. Disease activity was assessed during 6 months of follow-up. Potential relationships between those entry MMF-PK variables and clinical outcome were analyzed.
  
  
  RESULTS
  MMF controlled disease activity in 17 patients (successes) and failed to do so for 8 others (failures). For failures and successes, respectively, entry MPA areas under the time-concentration curve between 0 and 12 hours (AUC(0-12 h)) (medians: 37.7 vs 73.1 mg/h/L, P = 0.003) and MPA 12-hour trough concentrations (C(12 h)) (medians: 1.5 vs 3.7 mg/L, P = 0.008) were significantly lower, and inclusion MPAG/MPA C(12 h) ratios (medians: 18.7 vs 10.2, P = 0.02) were significantly higher. According to our receiver operating characteristics curve analysis, MPA C(12 h) was best able to discriminate a flare during follow-up (93% sensitivity, 85% specificity). A 3-mg/L cut-off had 92% negative-predictive value for developing a flare during follow-up.
  
  
  CONCLUSIONS
  For our SLE patients without renal manifestations, clinical flares developing under maintenance therapy were associated with steady-state inclusion MPA C(12 h) < 3 mg/L.
authors.affiliation: Laboratoire de Pharmacocinétique et Pharmacie Clinique EA2968, Université Victor Segalen Bordeaux 2, Hôpital Haut-Lévêque, CHU de Bordeaux, Avenue de Magellan, 33604 Pessac Cedex, France. sarah.djabarouti@chu-bordeaux.fr
authors.forename: Sarah
authors.initials: S
authors.lastname: Djabarouti
authors.forename: Dominique
authors.initials: D
authors.lastname: Breilh
authors.forename: Pierre
authors.initials: P
authors.lastname: Duffau
authors.forename: Estibaliz
authors.initials: E
authors.lastname: Lazaro
authors.forename: Carine
authors.initials: C
authors.lastname: Greib
authors.forename: Olivier
authors.initials: O
authors.lastname: Caubet
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Saux
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Pellegrin
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Viallard
mesh_terms: D000328:Adult; D019540:Area Under Curve; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000188:drug therapy*; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid