Influence of Metal Cations on Plasma Trough Concentration of Mycophenolic Acid and Its Glucuronide in Tacrolimus-Treated and Cyclosporine-Treated Kidney Transplant Recipients

Abstract

The aim of this study was to evaluate the plasma trough concentrations (C₀) of mycophenolic acid (MPA) and its major metabolite MPA 7-O-glucuronide (MPAG) in metal cation (MC)(−) (non-treated) and MC(+) (co-treated) patients who received tacrolimus (Tac) or cyclosporine (CyA). Fifty-nine Japanese stable kidney transplant recipients receiving immunosuppressive regimens containing mycophenolate mofetil (MMF) and a calcineurin inhibitor (CNI) were included in this study. Seven in the 25 patients receiving Tac and 8 in the 34 patients receiving CyA were treated with concomitant MCs administration. Multiple regression analysis revealed that concomitant MCs and CyA administration influenced MPA C₀. Their standardized partial regression coefficients were −0.29 and −0.41, respectively. Stratified analysis based on CNI treatment revealed that MPA C₀ decreased significantly by 56% with concomitant MCs administration in Tac-treated patients. There was no significant difference in MPA C₀ between the MC(−) and MC(+) groups in CyA-treated patients. With respect to MPAG C₀, MC(+) group tended to be lower by 26% than MC(−) group in Tac-treated patients. There was no significant difference in MPAG C₀ between the MC(−) and MC(+) groups in CyA-treated patients. Concomitant MCs administration did not affect the C₀ ratio of MPAG to MPA in either Tac- or CyA-treated patients. In conclusion, MCs co-administration decrease MPA C₀ in patients receiving Tac and may cause lower MPA exposure. There are little pharmacokinetic interactions between MMF and concomitant MCs in CyA-treated patients.