IMPDH- und MPA-Messungen zur Klärung der Interaktionen zwischen Mycophenolat-Natrium und dem Protonenpumpeninhibitor Pantoprazol nach primärer orthotoper Herztransplantation

In this prospective study we investigated the impact of the proton
pump inhibitor (PPI) pantoprazole on the bioavailability of
mycophenolic acid (MPA) after oral administration of enteric-coated
mycophenolate sodium (EC-MPS; Myfortic) in heart or lung transplant
recipients. Previously we demonstrated that pantoprazole reduces
the MPA exposure of mycophenolate mofetil (MMF; CellCept) by 34% in
area under the concentration-time curve (AUC). Because
gastrointestinal side-effects are common after organ
transplantation, we investigated the effect of PPI on MPA levels in
patients receiving EC-MPS. MPA plasma concentrations and inosine
monophosphate dehydrogenase (IMPDH) activity at baseline, 30
minutes and 1, 2, 3 and 4 hours were obtained from 21 patients.
These patients were treated with pantoprazole 40 mg once daily and
EC-MPS twice daily at a mean dose of 960 mg. Measurements were
repeated after pantoprazole withdrawal. MPA concentrations and
IMPDH activities did not reveal any significant difference during
PPI treatment and after withdrawal. MPA AUC, MPA C(max) (maximal
MPA concentration), the time until C(max) was reached (T(max)) and
IMPDH activity AUC all showed no significant difference. We did not
find an influence of pantoprazole on EC-MPS pharmacokinetics such
as we did for MMF in our previous investigation. A further
prospective, large, cross-over study is planned to support these
preliminary results. Given that MPA exposure by AUC correlates with
the incidence of acute rejection episodes and transplant
vasculopathy, the present findings may have clinical implications.