Trade names Neoral, Sandimmune
Routes of administration are oral, IV, and ophthalmic.
Undergoes hepatic metabolism with CYP3A4.
Half-life about 24 hours.
Undergoes biliary excretion.
An immunosuppressant drug widely used in organ transplantation to prevent rejection.
Reduces the activity of the immune system by interfering with the activity and growth of T cells.
Approved to prevent and treat graft-versus-host disease in bone-marrow transplantation and to prevent rejection of kidney, heart, and liver transplants.
Cyclosporine is a cyclic polypeptide that suppresses some humoral immunity and, to a greater extent, cell-mediated immune reactions such as delayed hypersensitivity, allograft rejection, experimental allergic encephalomyelitis, and graft versus host disease for various organs.
Approved for the treatment of rheumatoid arthritis and psoriasis, severe atopic dermatitis, Kimura’s disease, pyoderma gangrenosum, and chronic autoimmune urticaria,
Used as an ophthalmic emulsion for the treatment of dry eyes.
Used to help treat patients with acute severe ulcerative colitis that does not respond to steroids and as a treatment of posterior or intermediate uveitis.
Adverse drug reactions: convulsions, confusion, diarrhea, dyspnea, fever, hypertension, hyperkalemia, gingival hyperplasia, numbness and tingling, pancreatitis, pruritus, vomiting, hypercholesterolemia, peptic ulcers, nephrotoxicity, liver dysfunction, vulnerability to infection, neurotoxicity, increased risk squamous cell skin cancers, and hirsutism.
Binds to the cytosolic protein immunophilin of lymphocytes, especially T cells.
Cyclosporine inhibits calcineurin, which, under normal circumstances, is responsible for activating the transcription of interleukin 2.
Activation of the T-cell receptor in T- cells increases intracellular calcium, which acts via calmodulin to activate calcineurin.
Calcineurin then dephosphorylates the transcription factor nuclear factor of activated T-cells (NFATc), which moves to the nucleus of the T-cell and activates genes coding for IL-2 and other cytokines.
Cyclosporine prevents the dephosphorylation of NF-AT by binding to cyclophilin, and inhibits lymphokine production and interleukin release and, reduces function of effector T-cells.
Affects mitochondria by preventing its permeability transition pore from opening, inhibiting cytochrome c release, a potent apoptotic stimulation factor.
Extensively metabolized after ingestion with resulting metabolites include cyclosporin B, C, D, E, H, L, and others.
Metabolites have about 10% immunosuppressant activity of cyclosporine and are associated with higher nephrotoxicity.
Available as capsules, oral solution, topical ophthalmologic solution, and as a formulation for intravenous administration.
A possible neuroprotective agent in conditions such as traumatic brain injury blocking the formation of the mitochondrial permeability transition pore, which has been found to be associated with head injury and neurodegenerative diseases.
Decreases cardiac hypertrophy by affecting cardiac myocytes.
Can cause irreversible tubular injury.
A calcineurin inhibitor, blocks the process of T-cell activation through the T-cell receptor.
Daily doses that exceed 4 mg/kg are associated with nephropathy.
Can worsen hypertension, although infrequently causes new onset hypertension doing short course, intermittent therapy.
Can result in hyperlipidemia.
Topical ophthalomologic cyclosporine side effects include burning sensation, redness, discharge, watery eyes, eye pain, foreign body sensation, itching, stinging, and blurred vision.