Pharmacokinetics of mycophenolate mofetil for autoimmune disease in children.
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 micro gxh/ml, median time to maximum concentration was 60 min, and mean maximum concentration was 18.5+/-8.4 micro g/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) micro g/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.
Filler
Guido
G
Department of Pediatrics, Division of Nephrology, Children's Hospital of Eastern Ontario, University of Ottawa, 401 Smyth Road, K1H 8L1, Ottawa, Ontario, Canada. filler@cheo.on.ca
Hansen
Miriam
M
LeBlanc
Claire
C
Lepage
Nathalie
N
Franke
Doris
D
Mai
Ingrid
I
Feber
Janusz
J
D000293:Adolescent; D019867:Anti-Glomerular Basement Membrane Disease / Q000188:drug therapy; D016736:Antiphospholipid Syndrome / Q000188:drug therapy; D001327:Autoimmune Diseases / Q000188:drug therapy*; D002648:Child; D005260:Female; D014890:Granulomatosis with Polyangiitis / Q000188:drug therapy; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy; D008297:Male; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D009395:Nephritis, Interstitial / Q000188:drug therapy; D012074:Remission Induction; D016896:Treatment Outcome
D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid