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

Journal: Journal Of Clinical Rheumatology : Practical Reports On Rheumatic & Musculoskeletal Diseases
Published:
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
Joyce Hui Yuen, Tran, Jennifer Taylor, Kristi Truong, Xiaoqing Li, Liza Bermudez, Amy Starr, Andrew Eichenfield, Lisa Imundo, Anca Askanase