Session Time: 5:30pm-6:30pm
Presentation Time: 5:30pm-6:30pm
Location: Exhibit Hall E
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.
|Mean (SD)||p-value||Ratio(%)||90% CI|
To cite this abstract in AMA style:Rissling O, Glander P, Hambach P, Mai M, Brakemeier S, Klonower D, Halleck F, Singer E, Schrezenmeier E, Duerr M, Neumayer H, Budde K. No Pharmacokinetic Interaction Between Pantoprazole and Mycophenolic Acid in Renal Transplant Patents: A Randomized Crossover Study [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/no-pharmacokinetic-interaction-between-pantoprazole-and-mycophenolic-acid-in-renal-transplant-patents-a-randomized-crossover-study/. Accessed October 24, 2020.
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