CLINICAL IMMUNOSUPPRESSION - KIDNEY EARLY

B. Pons¹, X. Delavenne², T. Basset², M. Medhi³, N. Maillard³, C. Sauron³, F. Berthoux³, E. Alamartine³, C. Mariat^3
1Nephrology, Dialysis And Transplantation, Centre Hospitalier Universitaire Saint-Etienne, Saint Etienne/FRANCE, ²Laboratory Of Pharmacology, CHU Saint Etienne, Saint Etienne/FRANCE, ³Nephrology, Dialysis And Transplantation, CHU Saint Etienne, Saint Etienne/FRANCE

Body: Introduction There are no clear guidelines concerning the appropriate dose of mycophenolate acid (MPA) to be used in association with tacrolimus. When MPA is administered at a standard fixed dose in cyclosporine-treated patients, systemic underexposure is frequent during the first three months post-renal transplantation and is associated with the occurrence of acute rejection. We wanted to pharmacologically evaluate a novel dosing regimen of MPA in association with tacrolimus, consisting in the administration of an initial intensified dose of MPA followed by a gradual decrease over time. Methods Fifteen de novo tacrolimus-treated kidney transplant patients were administered mycophenolate sodium at the dose of 720 mg bid for the first week post-transplant, 540 mg bid until day 30, and then 360 mg bid until day 90. MPA exposure was evaluated by the 12 hours-area under MPA serum concentration versus time curve (AUC) determined at days 2, 7, 15, 30 and 90 post-transplant. Results Median MPA AUC was constantly within the therapeutic window of 30-60 mg.h/L throughout the three months of evaluation, with a proportion of patients having an adequate MPA exposure ranging from 57% to 71%. Interestingly, the lower limit of the therapeutic window was rapidly reached and more than 75% of patients had a MPA AUC over 30 mg.h/L at day 2 and day 7 post-transplant. No major adverse events related to the MPA administration occurred and no dose adjustment was necessary during the study. Conclusion We conclude that this intensified and decreasing dosing regimen of mycophenolate sodium is susceptible to quickly offer and sustain an optimal exposure to MPA in a very large majority of tacrolimus-treated kidney transplant patients. The added clinical benefit of such a regimen remains however to be evaluated.

Disclosure: All authors have declared no conflicts of interest.