Safety and steady-tate pharmacokinetics of a new oral formulation of cyclosporin A in renal transplant patients

The steady-state pharmacokinetics of a new oral formulation of cyclosporin A (Sandimmun Neoral, NOF, a microemulsion) was compared with those of the market formulation (Sandimmun, SIM) in stable renal transplant patients. Both formulations were administered as soft gelatin capsules every 12 h with doses adjusted to provide comparable trough concentrations (CminSS). Whole blood samples were obtained over a steady-state dosing interval (tau), and the cyclosporin A level was determined by a specific monoclonal RIA. Both formulations were well tolerated. The mean doses were 139 +/- 27 mg (SIM) vs. 120 +/- 19 mg (NOF), indicating a milligram dose-conversion factor of approximately 1:1 to yield comparable troughs. NOF exhibited a stronger correlation between AUCtauSS and CminSS (r2 = 0.821) compared with SIM (r2 = 0.288), due in part to less variability in the NOF profiles. Average increases of 39% in CmaxSS and 15% in AUCtauSS during treatment with NOF were not associated with any safety concerns over the 4-week exposure to Sandimmun Neoral, as evidenced by the absence of changes in blood pressure, hematologic and biochemical parameters (including serum creatinine and blood urea nitrogen, BUN) and ultrasound of the transplanted kidney.