DESCRIPTION
Cyclosporine is an immunosuppressant drug widely used in post-allogeneic 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, liver, lung, pancreas, bone marrow, and small intestine. Initially isolated from a Norwegian soil sample, Ciclosporin A, the main form of the drug, is a cyclic nonribosomal peptide of 11 amino acids produced by the fungus Beauveria nivea, and contains a single D-amino acid, which are rarely encountered in nature
INDICATIONS
The success of Cyclosporin A in preventing organ rejection was shown in liver transplants performed by Dr. Thomas Starzl at the University of Pittsburgh Hospital. The first patient, on March 9, 1980, was a 28-year-old woman. Cyclosporin was subsequently approved for use in 1983.
Cyclosporin is also used in psoriasis, severe atopic dermatitis, pyoderma gangrenosum and, infrequently, in rheumatoid arthritis and related diseases, although it is only used in severe cases. It is commonly prescribed in the US as an ophthalmic ointment for the treatment of dry eyes. It has been investigated for use in many other autoimmune disorders. Inhaled cyclosporine has been investigated to treat asthma and is being studied as a preventative therapy for chronic rejection of the lungs. Cyclosporin has also been used to help treat patients with ulcerative colitis that do not respond to treatment with steroids. This drug is also used as a treatment of posterior or intermediate uveitis with non-infective etiology.
Cyclosporin A has been investigated as a possible neuroprotective agent in conditions such as traumatic brain injury, and has been shown in animal experiments to reduce brain damage associated with injury. Cyclosporin A blocks the formation of the mitochondrial permeability transition pore, which has been found to cause much of the damage associated with head injury and neurodegenerative diseases.
PHARMACOKINETICS
- Oral, intravenous absorption
- Biliary excretion
MOLECULAR MECHANISM
SIDE EFFECTS
TOXICITY
In 1970, Borei at the Sandoz Laboratories in Basel, Switzerland, discovered and isolated Cyclosporine
from the soil fungus Tolypocladium infintimi gams during a search for antifungal agents. Although it was found to have only weak antibiotic activity, cyclosporine, also known as Cyclosporin A (CsA), was identified as a potent immunosuppressive agent in 1976. CsAs therapeutic effects in psoriasis were discovered fortuitously in 1979 by Mueller and Herrmann during a pilot study to investigate CsA efficacy in rheumatoid arthritis. These investiga tors observed that in patients who had psoriatic arthritis, the psoriasis improved with CsA treatment. Since 1979, more than 60,000 patients worldwide have been treated for psoriasis with CsA. The original formulation of CsA (Sandimmune) was approved for prophylaxis of organ rejection in the United States in 1983. Neoral, a more bioavailable and more consistently absorbed microemulsion formulation of CsA, was approved for prophylaxis of organ rejection in the United States in 1995. Neoral was approved for the treatment of rh
