Cyclosporine alters correlation between free and total mycophenolic acid in kidney transplant recipients in the initial phase.

WHAT IS KNOWN AND OBJECTIVE: The factors affecting the pharmacokinetics of free mycophenolic acid (MPA) and its phenolic glucuronide (MPAG) are still unclear. The aim of this study was to evaluate the influence of cyclosporine on the pharmacokinetics of free MPA and MPAG.

METHODS: Seventy-seven kidney transplant recipients (23 were in an initial phase and 54 in a stable phase; 41 were treated with cyclosporine and 36 with tacrolimus) were enrolled. Free and total MPA and MPAG were determined using HPLC. The correlations between free and total predose concentrations (C(0) ) of MPA or MPAG were evaluated separately in patients receiving calcineurin inhibitor medications.

RESULTS AND DISCUSSION: Serum concentration of albumin was lower in the initial phase than in the stable phase. A higher ratio of free MPAG C(0) to free MPA C(0) was observed in cyclosporine-treated than tacrolimus-treated kidney transplant recipients. Free MPA C(0) correlated weakly with total MPA C(0) in kidney transplant recipients treated with cyclosporine in the initial phase (ρ= 0·53, P = 0·06).

WHAT IS NEW AND CONCLUSION: Cyclosporine increased the ratio of free MPAG C(0) to free MPA C(0) and varied the free fraction of MPA in the hypoalbuminaemic kidney transplant recipients in the initial phase.