title: Monitoring of mycophenolate mofetil metabolites in children with nephrotic syndrome and the proposed novel target values of pharmacokinetic parameters.
abstract: 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 [MPAG]) 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 (Ctrough) and up to 12h afterward employing high-performance liquid chromatography. Dose-normalized MPA Ctrough and area under the concentration-time curve from 0 to 12h (AUC12) were within 0.29-6.47 μg/mL/600 mg/m(2) and 9.97-105.52 μg h/mL/600 mg/m(2), respectively. MPA Ctrough was twofold lower (p=0.024) in children with proteinuria recurrence. MPA, fMPA and MPAG concentrations correlated positively to respective AUC12. It may be suggested MMF metabolites monitoring in children with proteinuric glomerulopathies is justified by MPA Ctrough<2 μg/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 Ctrough>3 μg/mL may be considered as an efficient one to avoid proteinuria recurrence. Finally, MPA target AUC12 should exceed 60 μg h/mL to ensure the safe and effective treatment in children with nephrotic syndrome, however, the upper limit is still to be established.
authors.affiliation: Department of Physical Pharmacy and Pharmacokinetics, Poznan University of Medical Sciences, 6 Swiecickiego Street, 60-781 Poznan, Poland. Electronic address: jsobiak@ump.edu.pl.
authors.forename: Joanna
authors.initials: J
authors.lastname: Sobiak
authors.affiliation: Department of Physical Pharmacy and Pharmacokinetics, Poznan University of Medical Sciences, 6 Swiecickiego Street, 60-781 Poznan, Poland.
authors.forename: Matylda
authors.initials: M
authors.lastname: Resztak
authors.affiliation: Department of Pediatric Cardiology and Nephrology, Poznan University of Medical Sciences, 27/33 Szpitalna Street, 60-572 Poznan, Poland.
authors.forename: Danuta
authors.initials: D
authors.lastname: Ostalska-Nowicka
authors.affiliation: Department of Pediatric Cardiology and Nephrology, Poznan University of Medical Sciences, 27/33 Szpitalna Street, 60-572 Poznan, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Zachwieja
authors.affiliation: Department of Physical Pharmacy and Pharmacokinetics, Poznan University of Medical Sciences, 6 Swiecickiego Street, 60-781 Poznan, Poland.
authors.forename: Karolina
authors.initials: K
authors.lastname: Gąsiorowska
authors.affiliation: Department of Physical Pharmacy and Pharmacokinetics, Poznan University of Medical Sciences, 6 Swiecickiego Street, 60-781 Poznan, Poland.
authors.forename: Wiktoria
authors.initials: W
authors.lastname: Piechanowska
authors.affiliation: Department of Physical Pharmacy and Pharmacokinetics, Poznan University of Medical Sciences, 6 Swiecickiego Street, 60-781 Poznan, Poland.
authors.forename: Maria
authors.initials: M
authors.lastname: Chrzanowska
mesh_terms: D000293:Adolescent; D019540:Area Under Curve; D002648:Child; D002675:Child, Preschool; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008297:Male; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D009404:Nephrotic Syndrome / Q000188:drug therapy*
chemical_list: D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid
keywords: Free mycophenolic acid; Glomerulopathies; Mycophenolate mofetil (PubChem CID: 5281078); Mycophenolic acid; Mycophenolic acid (PubChem CID: 446541); Mycophenolic acid glucuronide; Mycophenolic acid glucuronide (PubChem CID: 6442661); Pharmacokinetics