Cyclosporin A

Abstract

Cyclosporin A is one of a group of biologically active metabolites produced by the fungus Tolypocladium inflatum. It is a non-polar cyclic oligopeptide with immunosuppressive and antifungal activity used to minimize rejection following organ transplantation. Administration is via the parenteral or oral route. Absorption after oral administration is variable and incomplete. In blood it is found in erythrocytes (50%), leukocytes (10%), and bound to plasma proteins (40%). Cyclosporin is metabolized in the liver by the cytochrome P-450 enzymes whose activity can be increased by inducers of hepatic enzymes. The primary excretion route is in bile. Clearance from blood is biphasic with a terminal half-life of 10 to 27 hours. The major adverse effect is dose-related nephrotoxicity which occurs in approximately a third of patients. The concentration difference between possible transplant rejection and toxicity is small. It has been suggested that whole blood measurements of 0.25-1 μg/ml or plasma concentrations of 0.05-0.2 μg/ml produce satisfactory immunosuppression and minimize adverse effects.