Cyclosporin

Cyclosporin

Cyclosporin, also spelled cyclosporine, is an immunosuppressant medication widely used in organ transplantation to prevent rejection. It is a cyclic polypeptide consisting of 11 amino acids and is produced by the fungus *Tolypocladium inflatum*. Cyclosporin has revolutionized transplant medicine since its discovery and introduction into clinical practice.

History

Cyclosporin was discovered in 1971 by Jean-François Borel, a Swiss scientist working for Sandoz (now Novartis). It was first isolated from a soil sample obtained in Norway. The drug was initially investigated for its antifungal properties, but its immunosuppressive effects were soon recognized, leading to its development as a medication to prevent organ rejection.

Mechanism of Action

Cyclosporin works by inhibiting the activity of calcineurin, a protein phosphatase involved in activating T-cells of the immune system. By binding to the cytosolic protein cyclophilin, cyclosporin forms a complex that inhibits calcineurin, thereby preventing the transcription of interleukin-2 (IL-2) and other cytokines essential for T-cell activation and proliferation.

Clinical Uses

Cyclosporin is primarily used to prevent organ rejection in kidney, liver, heart, and other organ transplants. It is also used in the treatment of certain autoimmune disorders, such as rheumatoid arthritis and psoriasis. In ophthalmology, cyclosporin is used in the form of eye drops to treat chronic dry eye disease.

Side Effects

The use of cyclosporin is associated with several side effects, including:

• Nephrotoxicity: Cyclosporin can cause kidney damage, which is dose-dependent and requires careful monitoring of kidney function.
• Hypertension: Patients on cyclosporin often experience elevated blood pressure.
• Hyperlipidemia: Increased levels of cholesterol and triglycerides can occur.
• Gingival hyperplasia: Overgrowth of gum tissue is a common side effect.
• Hirsutism: Excessive hair growth can be seen in some patients.

Drug Interactions

Cyclosporin is metabolized by the cytochrome P450 3A4 enzyme system in the liver. As a result, it can interact with a wide range of drugs, including:

• Antibiotics such as erythromycin and clarithromycin, which can increase cyclosporin levels.
• Antifungal agents like ketoconazole, which can also increase cyclosporin levels.
• Anticonvulsants such as phenytoin and carbamazepine, which can decrease cyclosporin levels.

Monitoring

Patients on cyclosporin require regular monitoring of blood levels to ensure therapeutic efficacy while minimizing toxicity. Kidney function, blood pressure, and lipid levels should also be monitored regularly.

Also see

• Immunosuppressive drug
• Organ transplantation
• Calcineurin inhibitor
• Autoimmune disease

CaptionSynonyms

Cyclosporin

Drug Information
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