Clinical research Pharmacokinetics of mycophenolic acid and its phenyl glucuronide metabolite in kidney transplant recipients with renal impairment Jolanta Kamińska1, Maciej Głyda2, Joanna Sobiak1, Maria Chrzanowska1 1Department of Physical Pharmacy and Pharmacokinetics, Poznan University of Medical Sciences, Poland 2Department of Transplantology, District Hospital, Poznań, Poland Submitted: 5 August 2010 Accepted: 25 October 2010 Arch Med Sci 2012; 8, 1: 88-96 DOI: 10.5114/aoms.2012.27287 Copyright © 2012 Termedia @ Banach A b s t r a c t Introduction: The aim of the study was to analyse the influence of renal impair- ment 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 main- tenance 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 func- tion (n = 17; creatinine clearance (Ccr) > 60 ml/min) and with renal impairment (n = 26; Ccr < 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 AUC0-4 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 AUC0-4 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. Key words: kidney transplantation, immunosuppressive agents, mycophenolate mofetil metabolites, pharmacokinetics, renal impairment. Introduction Mycophenolate mofetil (MMF, CellCept®) is the most widely used antiproliferative immunosuppressive drug in patients after solid organ transplantation, often co-administered with calcineurin inhibitors (CNI) and corticosteroids [1]. Pharmacologically inactive MMF after oral administration is rapidly and entirely hydrolysed into an active metabolite – mycophenolic acid (MPA). The MPA is a non-nucleoside, uncompetitive and reversible inosine monophosphate dehydrogenase inhibitor, which participates in guano- sine triphosphates de novo synthesis. As a consequence, MPA inhibits the Corresponding author: Maria Chrzanowska PhD Department of Physical Pharmacy and Pharmacokinetics Poznan University of Medical Sciences 6 Święcickiego 60-781 Poznan, Poland Phone: +48618546436 Fax: +48618546430 E-mail: mchrzan@ump.edu.pl