Cyclosporine (IPA: [ˈsaɪkləˌspɔrən]), ciclosporin (INN), or cyclosporin (former BAN), is an immunosuppressant drug. It is widely used 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, lung, pancreas, bone marrow and small intestine. Cyclosporine is a cyclic nonribosomal peptide of 11 amino acids (an undecapeptide) produced by the fungus Hypocladium inflatum gams, initially isolated from a Norwegian soil sample.^[1] CAS registry numbers are unique numerical identifiers for chemical compounds, polymers, biological sequences and alloys. ... The Anatomical Therapeutic Chemical Classification System is used for the classification of drugs. ... A chemical formula (also called molecular formula) is a concise way of expressing information about the atoms that constitute a particular chemical compound. ... The molecular mass of a substance (less accurately called molecular weight and abbreviated as MW) is the mass of one molecule of that substance, relative to the unified atomic mass unit u (equal to 1/12 the mass of one atom of carbon-12). ... In pharmacology, bioavailability is used to describe the fraction of an administered dose of medication that reaches the systemic circulation, one of the principal pharmacokinetic properties of drugs. ... The liver is one of the largest internal organs of the human body. ... The elimination half-life of a drug (or any xenobiotic agent) refers to the timecourse necessary for the quantity of the xenobiotic agent in the body (or plasma concentration) to be reduced to half of its original level through various elimination processes. ... Excretion is the biological process by which an organism chemically separates waste products from its body. ... The pregnancy category of a pharmaceutical agent is an assessment of the risk of fetal injury due to the pharmaceutical, if it is used as directed by the mother. ... Motto: none (formerly Advance Australia) Anthem: Advance Australia Fair Capital Canberra Largest city Sydney Official language(s) English (de facto)1 Government  â€¢ Queen  â€¢ Governor-General  â€¢ Prime Minister Const. ... The regulation of therapeutic goods, that is drugs and therapeutic devices, varies by jurisdiction. ... The International Phonetic Alphabet (IPA) is a system of phonetic notation devised by linguists to accurately and uniquely represent each of the wide variety of sounds (phones or phonemes) used in spoken human language. ... An International Nonproprietary Name (INN) is the official non-proprietary or generic name given to a pharmaceutical substance, as designated by the World Health Organization. ... A British Approved Name (BAN) is the official non-proprietary or generic name given to a pharmaceutical substance, as defined in the British Pharmacopoeia (BP). ... Immunosuppression is the medical suppression of the immune system. ... Oral medication A medication is a licenced drug taken to cure or reduce symptoms of an illness or medical condition. ... Link titleLink titleLink titleLink titleLink titleLink titleLink titleLink titleLink titleLink titleLink titleLink titleLink titleLink titleLink titleLink titleLink titleLink titleLink titleLink titleLink titleLink titleAn organ transplant is the transplantation of a whole or partial organ from one body to another (or from a donor site on the patients own body... The immune system is the system of specialized cells and organs that protect an organism from outside biological influences. ... Transplant rejection occurs when the immune system of the recipient of an transplant attacks the transplanted organ or tissue. ... A cycle is anything round, in the physical sense (e. ... Nonribosomal peptides (NRP) are a class of secondary metabolites, usually produced by microorganisms like bacteria and fungi. ... In chemistry, an amino acid is any molecule that contains both amino and carboxylic acid functional groups. ... Divisions Chytridiomycota Deuteromycota Zygomycota Glomeromycota Ascomycota Basidiomycota Fungus growing on a tree in Borneo A fungus (plural fungi) is a eukaryotic organism that digests its food externally and absorbs the nutrient molecules into its cells. ...

Naming

Although the international nonproprietary name is now ciclosporin, it is still referred to as cyclosporine in most scientific journals and medical publications.

Commercialisation

The drug is marketed by Novartis under the brand names Sandimmune, the original formulation, and Neoral for the newer microemulsion formulation. Generic cyclosporine preparations have been marketed by companies such as Sangstat, Abbott Laboratories and Gengraf. Since 2002 a topical emulsion of cyclosporine for treating keratoconjunctivitis sicca has been marketed under the trade name Restasis. Annual sales of cyclosporine are around $1 billion. Novartis International AG is a multinational pharmaceutical company based in Basel, Switzerland. ... Abbott Laboratories NYSE: ABT is a pharmaceuticals and health care company. ... For the Cusco album, see 2002 (album). ... A. Two immisicble liquids, not emulsified; B. An emulsion of Phase B dispersed in Phase A; C. The unstable emulsion progressively separates; D. The (purple) surfactant positions itself on the interfaces between Phase A and Phase B, stabilizing the emulsion An emulsion is a mixture of two immiscible (unblendable) substances. ... Keratoconjunctivitis sicca (KCS), also called keratitis sicca, xerophthalmia, dry eye syndrome, or simply dry eyes, is an eye disease caused by decreased tear production or increased tear film evaporation commonly found in humans and small animals. ...

Uses

The immuno-suppressive effect of cyclosporine was discovered on January 31, 1972, by employees of Sandoz (now Novartis) in Basle, Switzerland, in a screening test on immune-suppression designed and implemented by Hartmann F. Stähelin. Cyclosporine was subsequently approved for use in 1983. January 31 is the 31st day of the year in the Gregorian calendar. ... 1972 (MCMLXXII) was a leap year starting on Saturday (the link is to a full 1972 calendar). ... Sandoz Laboratories was a Swiss pharmaceutical company, best known for inventing LSD in 1938 and later marketing it as a psychiatric miracle drug under the trade name Delysid. ... Location within Switzerland Basel (British English traditionally: Basle and more recently Basel , German: Basel , French: Bâle , Italian: Basilea ) is Switzerlands third most populous city (166,563 inhabitants (2004); 690,000 inhabitants in the conurbation stretching across the immediate cantonal and national boundaries made Basel Switzerlands second-largest...

Apart from in transplant medicine, cyclosporine is also used in psoriasis and infrequently in rheumatoid arthritis and related diseases, although it is only used in severe cases. It has been investigated for use in many other autoimmune disorders. It is often taken in conjunction with corticosteroids. More recently, cyclosporine has begun to be used to help treat patients suffering from ulcerative colitis with positive results. Rheumatoid arthritis (RA) is a chronic, inflammatory autoimmune disorder that causes the immune system to attack the joints. ... Autoimmune diseases arise from an overactive immune response of the body against substances and tissues normally present in the body. ... In physiology, corticosteroids are a class of steroid hormones that are produced in the adrenal cortex. ...

Cyclosporine 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 ^[2]. Cyclosporine 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. Serving to protect neurons from injury or degeneration. ... Traumatic brain injury (TBI), traumatic injuries to the brain, also called acquired brain injury, intracranial injury, or simply head injury, occurs when a sudden trauma causes damage to the brain. ... This article is in need of attention from an expert on the subject. ... Brain damage or brain injury is the destruction or degeneration of brain cells. ... The mitochondrial permeability transition pore, or MPT pore, is a protein pore that is formed in the membranes of mitochondria under certain pathological conditions such as traumatic brain injury and stroke. ... Head injury is a trauma to the head, that may or may not include injury to the brain (see also brain injury). ... Neurodegenerative disease is a condition which affects the brain function. ...

Mode of action

Cyclosporine is thought to bind to the cytosolic protein cyclophilin (immunophilin) of immunocompetent lymphocytes, especially T-lymphocytes. This complex of cyclosporin and cyclophylin inhibits calcineurin, which under normal circumstances is responsible for activating the transcription of interleukin-2. It also inhibits lymphokine production and interleukin release and therefore leads to a reduced function of effector T-cells. It does not affect cytostatic activity. It has also an effect on mitochondria. Cyclosporine A prevents the mitochondrial PT pore from opening and inhibits thus cytochrome c release, a potent apoptotic stimulation factor. However, this is not the primary mode of action for clinical use but rather an important effect for research on apoptosis. Cyclophilins are proteins that bind to cyclosporin A, which is usually used to suppress rejection after internal organ transplants. ... T cells are a subset of lymphocytes that play a large role in the immune response. ... Calcineurin (CN) is a protein phosphatase also known as protein phosphatase 2B (PP2B). ... Interleukin-2 (IL2) is an interleukin, a type of biological response modifier that can improve the bodys natural response to disease. ... Lymphokines are a subset of Cytokines that are produced by immune cells. ... Interleukins are a group of cytokines that are expressed by white blood cells (leukocytes, hence the -leukin) as a means of communication (inter-). The function of the immune system depends in a large part on interleukins, and rare deficiencies of a number of them have been described, all featuring autoimmune... In cell biology, a mitochondrion is an organelle found in the cells of most eukaryotes. ... Cytochrome c (horse heart: PDB 1HRC) is a small heme protein found loosely associated with the inner membrane of the mitochondrion. ... Apoptosis In biology, apoptosis (from the Greek words apo = from and ptosis = falling, commonly pronounced ap-a-tow-sis[1]) is one of the main types of programmed cell death (PCD). ...

Adverse effects and interactions

Treatment may be associated with a number of potentially serious adverse drug reactions (ADRs) and adverse drug interactions. Cyclosporine interacts with a wide variety of other drugs and other substances including grapefruit juice, although there have been studies into the use of grapefruit juice to increase the blood level of cyclosporine. An adverse drug reaction (abbreviated ADR) is a term to describe the unwanted, negative consequences sometimes associated with the use of medications. ... Binomial name Citrus × paradisi Macfad. ...

ADRs can include gum hyperplasia, convulsions, peptic ulcers, pancreatitis, fever, vomiting, diarrhea, confusion, breathing difficulties, numbness and tingling, pruritus, high blood pressure, potassium retention and possibly hyperkalemia, kidney and liver dysfunction (nephrotoxicity & hepatotoxicity), and obviously an increased vulnerability to opportunistic fungal and viral infections. Hyperplasia (or hypergenesis) is a general term for an abnormal increase in the amount of the cells of an organ or tissue causing it to increase in size. ... This article is about the medical term, epileptic seizure, as distinct from psychogenic non-epileptic seizure. ... Peptic ulcer is usually a non-malignant ulcer of the stomach (called gastric ulcer) or duodenum (called duodenal ulcer). ... Pancreatitis is inflammation of the pancreas. ... See Fever for the Kylie Minogue album; Fever is also a song by Otis Blackwell. ... Vomiting (or emesis) is the forceful expulsion of the contents of ones stomach through the mouth. ... Diarrhea (American English) or diarrhoea (Commonwealth English) is a condition in which the sufferer has frequent and watery, chunky, or loose bowel movements (from the ancient Greek word διαρροή = leakage; lit. ... Look up Confusion in Wiktionary, the free dictionary Confusion can have the following meanings: Unclarity or puzzlement, e. ... Paresthesia (paraesthesia in British) is a sensation of tingling, pricking, or numbness of the skin with no apparent physical cause, more generally known as the feeling of pins and needles. ... Paresthesia (paraesthesia in British) is a sensation of tingling, pricking, or numbness of the skin with no apparent physical cause, more generally known as the feeling of pins and needles. ... An itch (Latin: pruritus) is a sensation felt on an area of skin that makes a person or animal want to scratch it. ... Blood pressure is the pressure exerted by the blood on the walls of the blood vessels. ... Hyperkalemia (hyper is high, kalium is the Latin name for potassium) is an elevated blood level (above 5. ... Nephrotoxicity is a poisonous effect of some substances, both toxins and medication, on the kidney. ... Hepatotoxicity (from hepatic toxicity) is chemical-driven liver damage. ... Infected (Podcast) is also the name of an internet radio podcast hosted by Martin Sargent. ...

External link

• PDF from Novartis describing Sandimmune

Notes

1. ↑  Pritchard, DI. 2005. "Sourcing a chemical succession for cyclosporin from parasites and human pathogens". Drug Discovery Today 10 [10]: 688-691 and Walter Sneader 2005. "Ciclosporin" in: "Drug Discovery - A History", John Wiley & Sons, pages: 298-299 (refs. page 315). An alternative species name, Tolypocladium inflatum, appears in a 2001 online publication by Harriet Upton entitled "Origin of drugs in current use: the cyclosporin story" (retrieved June 19, 2005).
2. ↑  Sullivan PG, Thompson M, and Scheff SW. 2000. "Continuous Infusion of Cyclosporin A Postinjury Significantly Ameliorates Cortical Damage Following Traumatic Brain Injury". Experimental Neurology. 161 [2]: 631-637.

See also

• tacrolimus