Abstract
P736 Aims: The determination of IMPDH activity is a pharmacodynamic (PD) parameter of MPA activity. Enteric-coated mycophenolate sodium (EC-MPS) has been developed to avoid the release of mycophenolic acid (MPA) into the stomach and allow direct delivery of the active agent via small intestinal absorption. This is the first study to compare pharmacokinetics (PK) and the PD response of both drugs under the maintenance immunosuppression with tacrolimus. Methods: In this open-label study, 16 renal transplant patients on MMF and Tacrolimus with or without corticosteroids were converted to EC-MPS, containing an equimolar amount of MPA. Full 12h PK- and PD-profiles were obtained in each patient on MMF following the 2-week open-label run-in period and with EC-MPS 14 days after conversion. For each profile, IMPDH activity, MPAG and MPA concentrations (HPLC) were determined in parallel. IMPDH activity in peripheral mononuclear cells was measured using a non-radioactive procedure. Results: Equimolar doses of both formulations resulted in similar (p=n.s.) Cmax (EC-MPS: 13,57±6,4 vs. MMF: 15,37±8,2ng/ml), and MPA exposure (AUC; EC-MPS: 36,40±15,9 vs. MMF: 33,5±9,6 μg∗h/ml). The MPAG exposure was significantly higher during the treatment with EC-MPS (AUC; EC-MPS: 652,5±407 vs. MMF: 551,1±377 μg∗h/ml). EC-MPS resulted in a significant (p<0.003) later Tmax (30 vs. 90 min). The lowest daytime IMPDH activity was comparable (EC-MPS: 5,94±3,4 vs. MMF: 4,16±2,0 nmol/h/mg, n.s.), as well as the inhibition (EC-MPS: 57±22 vs. MMF: 62±57%). The daytime average IMPDH activity as a measure of the overall PD response was also similar (EC-MPS: 9,9±2,5 vs. MMF: 9,3±2,2nmol/h/mg). Conclusions: Treatment with equimolar doses of MMF and EC-MPS in a tacrolimus based regimen results in an identical drug exposure and similar PD-response, despite minor differences in PK.
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