title: Use of Glucuronidated Mycophenolic Acid Levels for Therapeutic Monitoring in Pediatric Lupus Nephritis Patients.
abstract: OBJECTIVE
  Mycophenolate mofetil (MMF) is used to treat pediatric-onset lupus nephritis (pLN). Data are equivocal on the use of plasma mycophenolic acid (MPA) levels as a measure of efficacy and predictor of therapeutic outcomes in pLN. Glucuronidated MPA (MPA-G) is an inactive metabolite that is a marker of adequate absorption and normal metabolism of MMF. We evaluated the use of MPA and MPA-G levels in routine care of pLN.
  
  
  METHODS
  This was a retrospective study of pLN patients treated with MMF dosed at 600 mg/m. Clinical renal remission (CR) was defined as proteinuria of less than 500 mg/24 h. Midinterval MPA and MPA-G plasma levels were drawn during routine follow-up, approximately 6 hours after the previous dose of MMF. Steady-state levels of MPA were calculated using pharmacokinetics and compared with routine midinterval plasma MPA levels.
  
  
  RESULTS
  Seventeen pLN patients treated with MMF had MPA and MPA-G levels. Eleven patients were in CR; 6 were not in CR at the time of evaluation and had not responded to MMF after more than 3 months of therapy. The mean MPA level for patients in CR was 3.26 ± 2.02 μg/mL compared with 3.02 ± 1.76 μg/mL for patients not in CR. Three patients in CR did not have detectable levels of MPA. Calculated steady-state levels of MPA did not reflect the observed levels. Glucuronidated MPA levels were therapeutic (44.2 ± 26.7 μg/mL) in patients in CR, but low (29.88 ± 22 μg/mL) in patients not in CR (not statistically significant).
  
  
  CONCLUSIONS
  Midinterval plasma levels of MPA do not reflect predicted steady-state levels in pLN and do not correlate with clinical response. Midinterval plasma levels of MPA-G indicate adequate absorption and may correlate better with clinical pLN activity.
authors.affiliation: From the *Division of Pediatric Rheumatology, Cohen Children's Medical Center, Lake Success, NY; †Chicago College of Pharmacy, Midwestern University, Downers Grove, IL; and ‡Division of Pediatric Rheumatology, Morgan Stanley Children's Hospital of New York-Presbyterian, Columbia University Medical Center; §College of Pharmacy and Health Professions, St John's University, Jamaica; ∥Division of Rheumatology, New York-Presbyterian Hospital, Columbia University Medical Center, New York, NY.
authors.forename: Joyce S
authors.initials: JS
authors.lastname: Hui-Yuen
authors.forename: Tran
authors.initials: T
authors.lastname: Tran
authors.forename: Jennifer
authors.initials: J
authors.lastname: Taylor
authors.forename: Kristi
authors.initials: K
authors.lastname: Truong
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Li
authors.forename: Liza M
authors.initials: LM
authors.lastname: Bermudez
authors.forename: Amy J
authors.initials: AJ
authors.lastname: Starr
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Eichenfield
authors.forename: Lisa F
authors.initials: LF
authors.lastname: Imundo
authors.forename: Anca D
authors.initials: AD
authors.lastname: Askanase
mesh_terms: D000293:Adolescent; D002648:Child; D016903:Drug Monitoring / Q000379:methods*; D004791:Enzyme Inhibitors / Q000097:blood / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008181:Lupus Nephritis / Q000188:drug therapy*; D008297:Male; D009173:Mycophenolic Acid / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D012189:Retrospective Studies
chemical_list: D004791:Enzyme Inhibitors; D009173:Mycophenolic Acid