A new oral formulation of cyclosporine for early oral immunosuppressive therapy in liver transplant recipients.

CsA-ME is a new oral microemulsion formulation of CsA. Studies in stable liver grafted patients with cholestasis and subsequent poor absorption of the conventional cyclosporine formulation showed a substantial increase in CsA absorption after conversion to CsA-ME. To investigate its use in patients during the early course after liver transplantation we recruited 50 liver transplant recipients in two centers. During the first study phase A CsA-ME was administered to 20 patients in incremental doses after a short initial course of intravenous cyclosporine. During the second study phase B (30 patients) CsA-ME was administered from the time of transplantation. One year actual patient and graft survival of patients included in phase A and B of the trial was between 90% and 93.3%; 50% and 60% of the patients enrolled in phase A and phase B of the trial were free from rejection at month 3, respectively. Chronic rejection was diagnosed in one patient. No increase in the incidence of CsA related side effects was observed. The optimum CsA-ME starting dose was found to be 10 mg/kgbw/day for patients without external biliary diversion and 15 mg/kgbw/day for patients with a T tube in situ. Using these starting doses, 26 consecutive patients with external bile diversion via T tube were treated with CsA-ME from the day of transplantation. Intravenous CsA was necessary only in three patients. When CsA-ME absorption in patients with stable liver function was compared with that in patients with early liver dysfunction, no difference in the pharmacokinetic profiles was observed between the groups. Our results indicate that CsA-ME therapy is effective and well tolerated in liver graft recipients, even in patients with external biliary diversion during the early posttransplant phase. Thus, CsA-ME is a useful alternative to intravenous CsA treatment in these patients.