Monitoring of mycophenolate mofetil metabolites in children with nephrotic syndrome and the proposed novel target values of pharmacokinetic parameters

The aim of the study was to estimate target values of mycophenolate mofetil (MMF) pharmacokinetic parameters in children with proteinuric glomerulopathies by calculating the pharmacokinetic parameters of MMF metabolites (mycophenolic acid [MPA], free MPA [fMPA] and MPA glucuronide IMPAGI) and assessing their relation to proteinuria recurrence. One hundred and sixty-eight blood samples were collected from children, aged 3-18 years, diagnosed with nephrotic syndrome or lupus nephritis. MMF metabolites concentrations were examined before drug administration (C-trough) and up to 12 h afterward employing high-performance liquid chromatography. Dose-normalized MPA C-trough and area under the concentration-time curve from 0 to 12 h (AUC(12)) were within 0.29-6.47 mu g/mL/600 mg/m(2) and 9.97-105.52 mu g h/mL/600 mg/m(2), respectively. MPA C-trough was twofold lower (p = 0.024) in children with proteinuria recurrence. MPA, fMPA and MPAG concentrations correlated positively to respective AUC(12). It may be suggested MMF metabolites monitoring in children with proteinuric glomerulopathies is justified by MPA C-trough < 2 mu g/mL in patients at risk of the proteinuria recurrence. Such a recurrence is most probably caused by not sufficient MPA concentration during proteinuric glomerulopathies treatment. MPA C-trough > 3 mu g/mL may be considered as an efficient one to avoid proteinuria recurrence. Finally, MPA target AUC(12) should exceed 60 mu g h/mL to ensure the safe and effective treatment in children with nephrotic syndrome, however, the upper limit is still to be established. (C) 2015 Elsevier B.V. All rights reserved.