Mycophenolic acid (MPA) is used as an immunosuppressive agent in renal transplant (tx) patients (pts). 2 formulations are on the market: The prodrug Mycophenolate-Mofetil (MMF) and Enteric Coated Mycophenolate Sodium (EC-MPS). Pantoprazole (PAN) leads to an increased gastric pH which may influence MPA absorption.

In this single-centre, open, randomized, 4-sequence, 4-treatment crossover study the influence of PAN 40mg once in the morning on MPA AUC and Cmax after MMF + EC-MPS intake were analysed in cyclosporine treated renal tx pts (>6months post-tx). MMF dosing was 500-100mg b.i.d. (EC-MPS 360-720mg). Additionally a pharmacokinetic (PK) + pharmacodynamic (PD) profile was determined of the main metabolite MPAG and the target enzyme activity of IMPDH. Noncompartmental analysis was used for calculating PK+PD parameters. MPA PK parameters were dose-normalized to equimolar doses of MPA (dAUC; dCmax). Inhibitory Emax model was used for determining IC50.

20pts participated in the study after given written informed consent; 12/20pts (60%) received standard dosing. For statistical analysis full PK/PD profiles were available for 17/20pts (85%). Bioequivalence criteria were not fulfilled for simultaneous intake of PAN+MPA regardless of the formulation for dAUC+dCmax leading to highest dAUC/dCmax for EC-MPS+PAN and lowest for MMF+PAN. Significant changes in tmax were detected for MMF (median: 1; min:0.5-max:5.0)+ EC-MPS (3; 1.5-12.0) (p-value: 0.024) and for EC-MPS±PAN (EC-MPS+PAN: 2; 0.5-10.0) (p=0.040). PAN intake did not show any impact on MPAG PK for MMF±PAN (AUC: p=0.989) or the other treatment options. IMPDH activity was also not affected (Area under enzyme activity curve (¯o;mol*h/s*mol AMP): MMF±PAN: p=0.126). IC50 values for MPA+PAN remained <5.5¯o;g/ml.

PAN influences MPA PK regardless of the formulation but the impact of this interaction is considered as low as MPAG PK + IMPDH activity were not affected in stable renal tx pts.

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