SYSTEMIC AND RENAL HEMODYNAMIC PROFILES OF NEORAL® ONCE VERSUS TWICE DAILY DOSING - RESULTS FROM OLN-453 STUDY

Abstract

789 Chronic use of cyclosporine (CSA) is associated with systemic and intrarenal vasoconstriction. To evaluate the hemodynamic differences between two Neoral® CSA dosing regimens, we perform a prospective, randomized, pilot study comparing de-novo adult renal transplant patients, assigned to once (QD, n=10) vs twice-daily (BID, n=7) dosing. Groups were comparable in terms of age, gender, CSA and prednisone dose, cadaveric and regrafts, and HLA mismatches distribution. Total daily doses were similar during the twelve weeks. Pharmacokinetic studies and 12 hs ambulatory blood pressure monitoring were done at weeks 2, 4 and 12 after starting CSA. Additionally, GFR (Tc-99m DTPA) and ERPF(I-131 Hippuran) were measured 12 hs after the last CSA dose, at the same timepoints. Results at week 12 were: (Table) and (Figure)TableFigureAdditionally, the incidence of adverse effects (including the number of acute rejections) within the first 12 weeks was comparable between groups. Conclusions- Our pilot study showed that the use of Neoral® CSA once daily is associated with favorable (yet not statistically significant) systemic and renal hemodynamic profiles, when compared with a twice daily dosing regimen. Larger studies are needed to confirm these findings. The use of CSA once daily is currently not approved by the FDA. Study sponsored by Novartis Pharmaceuticals Co, East Hanover, NJ, USA.