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

ObjectivesThe 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 methodsKidney 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 (C0) ratios of MPA acyl glucuronide (AcMPAG) to MPA (AcMPAG/MPA) and MPA phenol glucuronide (MPAG) to MPA (MPAG/MPA) on CyA C0 or Tac C0 was evaluated.ResultsAcMPAG C0 and MPAG C0 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 C0 (r = 0.75, P < 0.01 and r = 0.81, P < 0.01, respectively), but not to Tac C0.ConclusionsCyA increased AcMPAG/MPA as well as MPAG/MPA in a concentration-dependent manner, suggesting that higher CyA may cause AcMPAG-related adverse reactions. Tac did not alter pharmacokinetics of MPA and its glucuronides.