Neoral in de novo liver transplantation: adequate immunosuppression without intravenous cyclosporine.
Absorption of cyclosporine from the traditional oral formulation Sandimmune (Novartis Pharma, Basel, Switzerland) is particularly unpredictable in the early stages after liver transplantation. The absorption of cyclosporine is influenced by liver function, postoperative paralytic ileus, and graft dysfunction. Oral absorption of cyclosporine from Sandimmune is also bile dependent; cholestasis and external biliary drainage are associated with low cyclosporine absorption. Postoperative administration of intravenous Sandimmune is therefore often necessary to obtain adequate immunosuppression, despite the increased risk of renal and neurological toxicity. A microemulsion formulation of cyclosporine, Neoral (Novartis), has been developed to overcome the problems of poor and variable absorption of cyclosporine from Sandimmune. Uptake of cyclosporine from Neoral is rapid and less dependent on bile secretion so that higher peak concentrations are reached and absorption is less variable than with Sandimmune. A review of several open studies in which Neoral was administered to liver transplant patients immediately after transplantation is presented. The results suggest that the use of Neoral as a primary immunosuppressive therapy provides adequate cyclosporine trough levels, minimizing or obviating the need for intravenous cyclosporine administration. In addition, Neoral appears to reduce the risk of acute rejection episodes compared with immunosuppressive regimens involving intravenous cyclosporine.
Levy
G A
GA
Toronto Hospital and University of Toronto, Ontario, Canada.
Rasmussen
A
A
Mayer
A D
AD
Jamieson
N V
NV
Neuhaus
P
P
D000042:Absorption; D001682:Biological Availability; D002986:Clinical Trials as Topic; D016572:Cyclosporine / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016031:Liver Transplantation / Q000276:immunology*
D007166:Immunosuppressive Agents; D016572:Cyclosporine