Name: Cyclosporine (Sandimmune)
Class: Immunosuppressant
Mechanism: Binds to calmodulin and a cytoplasmic cytophilin ® selective inhib. of transcription of IL-2 gene ® inhib. of IL-2 prod. & release from T4 cells, inhib. of proliferation of T8 cells, block of T4 activation of B cells.
Absorption: Oral ® highly variable and incomplete absorption.
Dist.: Large Vd. Binds in tissues. 60-70% contained in RBCs.
Metabolism.: Extensive hepatic Metabolism involving cyt. P450 enzymes. 17 Metabolismolites known. Drug levels monitored by RIA or HPLC.
Excretion, t½: Biliary excretion, minor renal excretion.
Toxicity/S.E.s: Nephrotoxicity (main toxicity), hepatotoxicity, hirsutism, gingival hyperplasia, neurotoxicity, altered coagulability. But little (if any) bone marrow suppression. Drug interactions—rifampin & phenobarbital ® induction of hepatic Metabolism. Erythromycin ® inhib. of hepatic Metabolism. Ketoconazole & amphotericin ® ¯ clearance.
Utility: Prolong organ transplants (1° use). Suppress cell-med. diseases. Possible benefit w/early treatment of IDDM.
Special Features: