Néoral® en transplantation hépatique

Abstract

Intestinal absorption of the microemulsion formulation of cyclosporin, Neoral®, unlike that of the conventional formulation, Sandimmun®, is relatively independent of factors such as the presence of bile acids, pancreatic enzymes and food. The consequent improvement in pharmacokinetic parameters, bioavailability and interindividual variability has particular advantages in liver transplantation. The first situation in which Neoral® may have a significant advantage over Sandimmun® is immediately after liver transplantation, when oral administration (which is not possible with Sandimmun®) is desirable because i) intravenous administration of cyclosporin may lead to increased toxicity and ii) the switch from intravenous to oral administration may cause a fall in blood cyclosporin concentration, with the consequent risk of rejection. In 4 of the 5 series comparing Neoral® and Sandimmun® de novo after liver transplantation, a significant reduction of the rejection rate in favour of Neoral® was observed, without significant differences in nephrotoxicity or neurotoxicity. The second situation in which Neoral® may have a particular advantage is in patients with impaired intestinal absorption, e.g. those with cystic fibrosis, in whom oral administration of Neoral® twice daily is usually successful. This finding may extend to other patients with limited cyclosporin absorption, such as young children and patients with cholestasis and gastroparesis. The third situation to consider is conversion from Sandimmun® to Neoral® some time after transplantation, where the improved pharmacokinetics of Neoral® may lead to reduced rates of acute and chronic rejection and possibly to a reduction in adverse effects. In patients converted to Neoral® more than 6 months after transplantation, the improved bioavailability necessitated a dosage reduction of 15 to 20%, particularly in those patients who were receiving relatively high dosages of Sandimmun®, and the incidence of adverse effects was not increased. Finally, there is the issue regarding discontinuation of corticosteroids in patients receiving Neoral® after liver transplantation. A pilot study has shown that this can be achieved more rapidly with Neoral® than with Sandimmun®.