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

Wolf, Christine (2013): IMPDH- und MPA-Messungen zur Klärung der Interaktionen zwischen Mycophenolat-Natrium und dem Protonenpumpeninhibitor Pantoprazol nach primärer orthotoper Herztransplantation. Dissertation, LMU München: Faculty of Medicine

Abstract

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.

• Item Type: Theses (Dissertation, LMU Munich)
• Keywords: Mycophenolat-Natrium,Pantoprazol,IMPDH,MPA,Herztransplantation
• Subjects: 600 Technology, Medicine; 600 Technology, Medicine > 610 Medical sciences and medicine
• Faculties: Faculty of Medicine
• Language: German
• Date of oral examination: 18. July 2013
• 1. Referee: Kofler, Sieglinde
• Signature of the printed copy: 0700/UMD 15497