Cyclosporine

Cyclosporine is an immunosuppressant drug. It is used post-allogenic organ transplant to reduce the activity of the patient's immune system and so the risk of organ rejection. It has been studied in transplants of skin, heart, kidney, lung, pancreas, bone marrow and small intestine.

It is also an antipsoriatic[?] and an antirheumatic[?], although it is only used in severe cases. It has been investigated in connection with a great many diseases. It is often taken in conjunction with corticosteroids.

The drug is sold by Novartis under the brand names Sandimmune® and Neoral®. Generic cyclosporine drugs have been produced by Sangstat, Abbott Laboratories and Gengraf. Annual sales of cyclosporine are around $1 billion.

The mechanism of cyclosporine is unclear. It is believed to operate through inhibiting immunocompetent lymphocytes[?], especially T-lymphocytes, by binding proteins to the cystol and disrupting the transcription of IL-2. It also inhibits lymphokine production and interleukin[?] release. It does not effect cytostatic activity.

Treatment has a number of potentially serious side effects and has adverse interactions with a wide variety of other drugs and other materials including grapefruit, although there have been studies to improve the blood level of cyclosporine with grapefruit juice. Side effects can include gum hyperplasia, convulsions, peptic ulcers, pancreatitis, fever, vomiting, diarrhea, confusion, breathing difficulties, numbness and tingling, pruritus, high blood pressure, kidney and liver disfunction, potassium retention and possibly hyperkalemia, hepatotoxicity, nephrotoxicity, and obviously an increased vulnerability to opportunistic fungal and viral infections.

Cyclosporine was discovered in 1970 in a Norwegian soil fungus by Jean F. Borel at Sandoz laboratories and it was approved for use in 1983. It is a cyclic polypeptide produced as a metabolite by Beauveria nive and consists of eleven amino acids. The chemical name of cyclosporine is [R-[R^*,R^*-(E)]]-cyclic(L-alanyl-D-alanyl-N-methyl-L-leucyl-N-methyl-L-leucyl-N-methyl-L-valyl-3-hydroxy-N,4-dimethyl-L-2-amino-6-octenoyl-L-α-amino-butyryl-N-methylglycyl-N-metyl-L-leucyl-L-valyl-N-methyl-L-leucyl) and the empirical formula is C₆₂H₁₁₁N₁₁O₁₂.

Compare with tacrolimus.

External link PDF at Novartis (http://www.pharma.us.novartis.com/product/pi/pdf/sandimmune.pdf)