Use of Glucuronidated Mycophenolic Acid Levels for Therapeutic Monitoring in Pediatric Lupus Nephritis Patients

• Published in: Journal of clinical rheumatology Vol. 22; no. 2; pp. 75 - 79
• Main Authors: Hui-Yuen, Joyce S, Tran, Tran, Taylor, Jennifer, Truong, Kristi, Li, Xiaoqing, Bermudez, Liza M, Starr, Amy J, Eichenfield, Andrew H, Imundo, Lisa F, Askanase, Anca D
• Format: Journal Article
• Language: English
• Published: United States Copyright Wolters Kluwer Health, Inc. All rights reserved 01-03-2016
• Subjects: Adolescent; Child; Drug Monitoring - methods; Enzyme Inhibitors - blood; Enzyme Inhibitors - therapeutic use; Female; Humans; Lupus Nephritis - drug therapy; Male; Mycophenolic Acid - blood; Mycophenolic Acid - pharmacokinetics; Mycophenolic Acid - therapeutic use; Retrospective Studies
• ISSN: 1076-1608; 1536-7355
• DOI: 10.1097/RHU.0000000000000357

BACKGROUND/OBJECTIVESMycophenolate 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.
METHODSThis 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.
RESULTSSeventeen 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).
CONCLUSIONSMidinterval 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.