CYCLOSPORINE METABOLITE PHARMACOKINETICS AND TOLERABILITY IN STABLE HEPATIC ALLOGRAFT RECIPIENTS COMPARING SANGCYA™ AND NEORAL® ORAL SOLUTIONS

Abstract

107 We evaluated the pharmacokinetics (PK) of cyclosporine (CyA) and its metabolites, measured by HPLC, and assessed the clinical tolerability after long-term administration of SangCya and Neoral in stable liver transplant (LT) recipients. Bioequivalence has been demonstrated between SangCya and Neoral in this patient population. Methods: SangCya and Neoral were administered in a randomized, double-blind, 2-period crossover study (Part I). Each period consisted of 7 days of SangCya or Neoral at the same dosage. PK of CyA and its metabolites were measured using an HPLC assay. After Day 15, the second assigned formulation was administered for 12 months in a blinded fashion for evaluation of long-term tolerability (Part II). Results: 26 patients were enrolled and 18 have completed 6-month follow-up. At enrollment, age (mean ±SD) was 53±10 years, and time posttransplant was 4.4±2.0 years. Metabolite data are available for the first 8 patients. Mean PK parameters of CyA, AM1 and AM9 are shown below. There were no significant differences (p>0.05, Anova) between SangCya and Neoral in PK of CyA or its metabolites (AM1, AM9, AM1c, AM4n). (Table)TableThere have been no graft losses or acute or allograft rejections during the 6-months following enrollment (Part II). Mean±SD CyA trough blood concentrations, serum creatinine levels, ALT, and bilirubin were similar (p>0.05) between patients receiving SangCya and Neoral at 6 months: (Table)TableConclusions: SangCya and Neoral demonstrate comparable steady-state PK of CyA and its metabolites, as well as similar clinical tolerability in stable LT recipients. The results suggest that these two CyA formulations are interchangeable. Funded by SangStat Medical Corporation, Menlo Park, CA