Cyclosporine concentration-dependent increase in concentration ratio of mycophenolic acid acyl and phenol glucuronides to mycophenolic acid in stable kidney transplant recipients

Objectives: The aim of this study was to evaluate the influence of cyclosporine (CyA) and tacrolimus (Tac) on the pharmacokinetics of mycophenolic acid (MPA) and its glucuronides. Design and methods: Kidney transplant recipients treated with mycophenolate mofetil and CyA (n=18) or Tac (n=17) in the stable phase were enrolled. The dependence of the trough concentration (CO) ratios of MPA acyl glucuronide (AcMPAG) to MPA (AcMPAG/MPA) and MPA phenol glucuronide (MPAG) to MPA (MPAG/MPA) on CyA C-0 or Tac C-0 was evaluated. Results: AcMPAG C-0 and MPAG C-0 were significantly higher in CyA- than Tac-treated recipients (P=0.04 and 0.02, respectively). AcMPAG/MPA and MPAG/MPA were significantly correlated to CyA C-0 (r=0.75, P<0.01 and r=0.81, P<0.01, respectively), but not to Tac C-0. Conclusions: CyA increased AcMPAG/MPA as well as MPAG/MPA ill a concentration-dependent manner, suggesting that higher CyA may cause AcMPAG-related adverse reactions. Tac did not alter pharmacokineties of MPA and its glucuronides. (C) 2008 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.