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 (C(0)) 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 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.