cyclosporin

Cyclosporin, also spelled cyclosporine, is a cyclic peptide immunosuppressant produced by the fungus Tolypocladium inflatum. It was developed for clinical use in organ transplantation and for certain autoimmune diseases. Cyclosporin works by binding to the intracellular protein cyclophilin to form a complex that inhibits calcineurin, a phosphatase required for the activation of transcription factors that drive interleukin-2 and other cytokine production. This suppression of T-cell activation reduces the immune response.

The main clinical use of cyclosporin is to prevent rejection of transplanted organs, including kidney, liver, and heart. It is also employed, sometimes in combination with other therapies, for autoimmune conditions such as psoriasis, rheumatoid arthritis, inflammatory bowel disease, and certain nephrotic syndromes that are resistant to conventional treatment. Formulations vary in bioavailability; non-modified and modified (microemulsion) products exist, and dosing must be individualized and guided by trough blood levels. Cyclosporin is extensively metabolized by the hepatic enzyme system CYP3A4 and is excreted mainly in the bile. Interactions with strong CYP3A inhibitors or inducers can markedly alter drug exposure, necessitating careful monitoring.

Adverse effects are common and can be dose-related. Nephrotoxicity is the most important concern, along with hypertension, hyperkalemia, and hyperlipidemia. Other frequent effects include tremor, hirsutism, gingival hyperplasia, and hepatotoxicity. Cyclosporin increases the risk of infections and certain malignancies due to its immunosuppressive action, and it requires ongoing clinical and laboratory monitoring.