Introduction : 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.
Material and 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 (AUC0-4 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 (C₀) for MPAG compared to patients with normal renal function and increased MPA C₀. 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 C₀ 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.