Pharmacokinetics of mycophenolate mofetil for autoimmune disease in children

Abstract

This study describes the pharmacokinetics of mycophenolate mofetil (MMF) in 15 pediatric patients with vasculitis and connective tissue disease involving the kidney. Patients included 10 with systemic lupus erythematosus (SLE), 1 with antiphospholipid antibody syndrome, 2 with Wegener granulomatosis, and 1 each with Goodpasture syndrome, Henoch-Schönlein-associated nephritis, and 1 with severe tubulointerstitial nephritis and uveitis. All patients were treated with steroids and additional therapy prior to treatment with MMF, which was administered for a median of 491 days. Mean starting dose of MMF was 974±282 mg/m 2 in two divided doses. Pharmacokinetic monitoring of the active compound of MMF, mycophenolic acid (MPA), was performed using an EMIT assay. The mean MPA AUC after a median of 39 days was 61.8±31.0 µg×h/ml, median time to maximum concentration was 60 min, and mean maximum concentration was 18.5±8.4 µg/ml. At last follow-up, mean MMF dose was 900±341 mg/m 2 per day, and mean trough MPA concentration was 3.1±1.1 (range 0.6-4.6) µg/ml. Therapy was effective in inducing remission in 4 of 9 patients with active disease. Only 1 of the 5 other patients relapsed. All 6 patients with controlled disease maintained remission. There were few side effects: one episode each of diarrhea and leukocytopenia and two viral infections. We conclude that MMF at 900 mg/m 2 per day appears to be effective in these patients.

Development and validation of limited sampling strategy equation for mycophenolate mofetil in children with systemic lupus erythematosus

“…[916] We also observed a similar correlation in our study. However, from our data 61.5% of our patients would have an incorrect dose change if only MPA trough (therapeutic goal: 1–5 μg/ml) was used as a replacement for MPA AUC (0-12) (therapeutic goal we used was 30–60 mg.h/L).…”

“…suggested that the trough concentration is a clinically important time point in MPA monitoring and defined a target trough C troughss concentration between 1 and 5 μg/ml in children with autoimmune disease. [16] In comparison, the range of trough concentrations (0.7–5.35 μg/ml) measured in our study was not significantly different. However, it needs to be mentioned that the median ± SD dose used in their study was 25.2 ± 10.6 mg/kg in comparison to the median ± SD of 38.89 ± 9.48 mg/kg used in our patients.…”

Mycophenolic Acid Differentially Impacts B Cell Function Depending on the Stage of Differentiation

“…In the clinic, the steady-state C max for MPA in serum of patients with lupus nephritis has been reported to be 21 μg/ml (66 μM) (29), the C max of MMF in children with autoimmunity, including SLE, is reported to be in the same range, 18.5 μg/ml (28), and the C max of MMF for patients with SLE was found to be 16.6 μg/ml (30). A similar range for transplant patients was reported (27).…”

Treatment of Complicated Henoch-Schönlein Purpura with Mycophenolate Mofetil: A Retrospective Case Series Report

“…There were few side effects including diarrhea and leukocytopenia in one case and viral infections in two cases. They conclude that MMF at 900 mg/m 2 per day appears to be effective in these patients [19]. …”