title: Pharmacokinetics of mycophenolic acid and its phenyl glucuronide metabolite in kidney transplant recipients with renal impairment.
abstract: BACKGROUND
  The aim of the study was to analyse the influence of renal impairment on the pharmacokinetic parameters (PK) of mycophenolic acid (MPA) and its glucuronide metabolite (MPAG) in renal transplant recipients.
  
  
  METHODS
  The study included 43 adult patients during the maintenance period (> 6 months) following renal transplantation, treated with mycophenolate mofetil (MMF), calcineurin inhibitors (CNI) (tacrolimus or cyclosporine) and steroids. The study compared patients with normal renal function (n = 17; creatinine clearance (C(cr)) > 60 ml/min) and with renal impairment (n = 26; C(cr) < 60 ml/min). Areas under the 4-h curve (AUC(0-4 h)) of MPA and MPAG were determined using a validated HPLC method.
  
  
  RESULTS
  The renal impairment group showed significantly increased AUC(0-4 h) and pre-dose (C(0)) for MPAG compared to patients with normal renal function and increased MPA C(0). However, there was no significant difference in MPA AUC(0-4 h) between patients with renal impairment and patients with normal renal function. In multivariate analysis some MPA and MPAG PK parameters were correlated with sex, CNI co-administered and body weight.
  
  
  CONCLUSIONS
  Although MPAG is an inactive metabolite, its accumulation in patients with renal impairment can be unfavourable. The results of our study indicate that solely MPA C(0) determination in patients receiving MMF may be insufficient in clinical practice because of great inter-patient variability of this PK parameter caused mainly by enterohepatic recirculation.
authors.affiliation: Department of Physical Pharmacy and Pharmacokinetics, Poznan University of Medical Sciences, Poland.
authors.forename: Jolanta
authors.initials: J
authors.lastname: Kamińska
authors.forename: Maciej
authors.initials: M
authors.lastname: Głyda
authors.forename: Joanna
authors.initials: J
authors.lastname: Sobiak
authors.forename: Maria
authors.initials: M
authors.lastname: Chrzanowska