title: Randomized crossover study to assess the inter- and intrasubject variability of morning mycophenolic acid concentrations from enteric-coated mycophenolate sodium and mycophenolate mofetil in stable renal transplant recipients.
abstract: The delayed release of mycophenolic acid (MPA) from enteric-coated mycophenolate sodium (EC-MPS, myfortic®) may have an impact on the variability of MPA trough (C0 h) levels. A randomized, two-period crossover study was performed in 24 maintenance renal transplants to evaluate the inter- and intrasubject variability of MPA predose levels from EC-MPS and mycophenolate mofetil (MMF, CellCept®), both in combination with cyclosporine. Patients received EC-MPS (720 mg b.i.d.) and MMF (1000 mg b.i.d.) for a period of 21 d each. MPA plasma levels were measured over the final seven consecutive days at -1, 0, 1, 2, and 3 h after the morning MPA dose. Intersubject coefficients of variation (%CV) for MPA troughs were 47.5% (95% CI, 34.1-80.3) and 54.4% (40.0-86.8) for EC-MPS and MMF, respectively; intrasubject %CVs were 62.7% (55.1-72.9) and 42.8% (37.9-49.2). High MPA C0 h levels>10 μg/mL were rarely observed with both EC-MPS (1.8%) and MMF (0.6%). Mean MPA area under the curve (AUC)0-3 h was comparable between treatments, while MPA C0 h was on average 46% higher with EC-MPS. In conclusion, predose MPA trough level monitoring appears of limited value during EC-MPS and MMF therapy given the large intrasubject variability in MPA C0 h levels with both treatments.
authors.affiliation: Hospital do Rim e Hipertensao, Universidade Federal de Sao Paulo, Sao Paulo, SP, Brazil. heliotedesco@hrim.com.br
authors.forename: Helio
authors.initials: H
authors.lastname: Tedesco-Silva
authors.forename: Claudia R
authors.initials: CR
authors.lastname: Felipe
authors.forename: Sung I
authors.initials: SI
authors.lastname: Park
authors.forename: Paula G
authors.initials: PG
authors.lastname: Pinheiro-Machado
authors.forename: Riberto
authors.initials: R
authors.lastname: Garcia
authors.forename: Alan
authors.initials: A
authors.lastname: Slade
authors.forename: Robert
authors.initials: R
authors.lastname: Schmouder
authors.forename: Jose O
authors.initials: JO
authors.lastname: Medina-Pestana
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019540:Area Under Curve; D001682:Biological Availability; D018592:Cross-Over Studies; D005260:Female; D006085:Graft Survival; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics*; D016030:Kidney Transplantation; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000097:blood* / Q000493:pharmacokinetics; D013608:Tablets, Enteric-Coated; D014018:Tissue Distribution; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D013608:Tablets, Enteric-Coated; D009173:Mycophenolic Acid