title: Mycophenolic acid area under the curve correlates with disease activity in lupus patients treated with mycophenolate mofetil.
abstract: OBJECTIVE
  Mycophenolic acid (MPA) is the active metabolite of mycophenolate mofetil (MMF), which is widely used to treat systemic lupus erythematosus (SLE). In transplantation, MPA area under the plasma concentration-time curve from 0 to 12 hours (MPA AUC(0-12)) is correlated with clinical outcome. We undertook the present study to assess possible relationships between SLE activity and MPA AUC(0-12).
  
  
  METHODS
  Using a Bayesian estimator, MPA AUC(0-12) was determined in 71 consecutive SLE patients (61 women and 10 men; mean +/- SD age 34 +/- 10 years) receiving a stable MMF dose. On the same day, SLE activity was assessed using the SLE Disease Activity Index (SLEDAI; active disease defined as a SLEDAI score > or = 6) and the British Isles Lupus Assessment Group (BILAG) index (active disease defined as BILAG A or B).
  
  
  RESULTS
  Two groups were studied: patients with active SLE (mean +/- SD SLEDAI score 11.6 +/- 4.4; n = 26) and patients with inactive SLE (mean +/- SD SLEDAI score 1.9 +/- 1.6; n = 45). MPA AUC(0-12) correlated weakly with the dose of MMF (r = 0.33, P = 0.005). Mean +/- SD MPA AUC(0-12) in the group with active SLE was significantly lower than that in the group with inactive SLE (26.8 +/- 13.6 microg.hour/ml versus 46.5 +/- 16.3 microg.hour/ml; P < 0.0001). MPA AUC(0-12) was negatively correlated with the SLEDAI (r = -0.64, P < 0.0001). In multivariate analysis, MPA AUC(0-12) was the sole parameter associated with SLE activity (odds ratio 0.89 [95% confidence interval 0.83-0.96], P = 0.002). The MPA AUC(0-12) threshold value of 35 microg.hour/ml was associated with the lowest risk of active SLE.
  
  
  CONCLUSIONS
  Our data show that SLE activity is strongly correlated with MPA AUC(0-12). An individualized dosing regimen of MMF, with a target AUC(0-12) of 35 microg.hour/ml, should be considered for SLE patients.
authors.affiliation: Pitié-Salpêtrière Hospital, Paris, France.
authors.forename: Noël
authors.initials: N
authors.lastname: Zahr
authors.forename: Laurent
authors.initials: L
authors.lastname: Arnaud
authors.forename: Pierre
authors.initials: P
authors.lastname: Marquet
authors.forename: Julien
authors.initials: J
authors.lastname: Haroche
authors.forename: Nathalie
authors.initials: N
authors.lastname: Costedoat-Chalumeau
authors.forename: Jean-Sébastien
authors.initials: JS
authors.lastname: Hulot
authors.forename: Christian
authors.initials: C
authors.lastname: Funck-Brentano
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Piette
authors.forename: Zahir
authors.initials: Z
authors.lastname: Amoura
mesh_terms: D000328:Adult; D019540:Area Under Curve; D005260:Female; D006304:Health Status; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D011446:Prospective Studies; D012720:Severity of Illness Index
chemical_list: D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid