HEART

A. Dösch¹, S. Müller², S. Celik¹, M. Konstandin¹, P. Ehlermann¹, A. Koch³, H.A. Katus¹, T.J. Dengler^1
1Department Of Cardiology, University of Heidelberg, Heidelberg/GERMANY, ², University of Heidelberg, Heidelberg/GERMANY, ³Department Of Cardiac Surgery, University of Heidelberg, Heidelberg/GERMANY

Body: Background
Proton pump inhibitors (PPIs) are often prescribed for gastrointestinal discomfort after heart transplantation (HTX). This study investigates the impact of PPI use on mycophenolate acid (MPA)pharmacokinetics in heart transplant recipients receiving mycophenolate mofetil (MMF) and a calcineurin inhibitor (tacrolimus [TAC]/cyclosporine A [CsA]) or mTOR inhibitor(sirolimus/everolimus).
Patients and methods
Abbreviated MPA-AUCs (area under the curve, 0, 30 and 120 min after morning intake) were consecutively obtained in 19 patients on a PPI (initial examination) and thereafter after PPI discontinuation(follow-up). Mean patient age was 58.2 ± 8.8 years and mean time post HTX was 2.3 ± 4.0 years.
Results
At initial examination mean daily MMF dose was 2.2 ± 0.8 g vs. 2.1 ± 1.1 g at follow-up (p=ns). Mean pre-dose (C0) MPA serum concentrations were insignificantly lower with PPIcomedication (2.5 ± 2.2 mg/l vs. 2.8 ± 1.7 mg/l, p=ns). Dose-adjusted abbreviated MPA-AUCs (adapted to morning dose) were significantly lower during PPI therapy (45.2 ± 20.3 vs.65.2 ± 38.8 mg*h/l, p=0.02) and a clear trend toward lower abbreviated total MPA-AUCs during PPI comedication was seen (44.5 ± 14.7 vs. 54.2 ± 17.2 vs. mg*h/l, p=0.07).
Conclusions
Patients with PPI comedication show significantly lower dose-adjusted MPA AUCs. Therapeutic drug monitoring with limited sampling strategies allows determination of MPA drug exposure in patientsafter HTX, is clinically feasible, and should be routinely repeated especially after PPI discontinuation.

Disclosure: All authors have declared no conflicts of interest.