Ciclosporin: Difference between revisions

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Chemical structure of cyclosporine. Chemical structure of cyclosporine. Ciclosporin
Empiric formula	C₆₂H₁₁₁N₁₁O₁₂
Molecular weight	1202.61
Bioavailability	?
Metabolism	Liver
Elimination half life	19 hours
Excretion	Bile
ATC code	L04AA01
Pregnancy category	C (USA) C (Aus)

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 companies such as Sangstat, Abbott Laboratories and Gengraf. Annual sales of cyclosporine are around $1 billion.

Cyclosporine is thought to bind to the cytosolic protein Cyclophylin (Immunophylin)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 IL-2. It also inhibits lymphokine production and interleukin release and therefore leads to a reduced function of effector T-cells. 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-methyl-L-leucyl-L-valyl-N-methyl-L-leucyl) and the empirical formula is C₆₂H₁₁₁N₁₁O₁₂.

Compare with tacrolimus.

External link

PDF at Novartis

Recent evidence indicates that cyclosporine A may prevent tolerance induction by its inhibition of calcineurin

@@ Line 1: / Line 1: @@
+{| border="1" cellpadding="2" cellspacing="0" width="250px" align="right" style="border-collapse:collapse;"
+|-
+|bgcolor="#ffffff" align="center" colspan=2|[[Image:Cyclosporine.png|center|200px|Chemical structure of cyclosporine.]]<br><small>Ciclosporin</small>
+|-
+|bgcolor="#efefef"|Empiric formula
+|bgcolor="#dfefff"|C<sub>62</sub>H<sub>111</sub>N<sub>11</sub>O<sub>12</sub>
+|-
+|bgcolor="#efefef"|[[Molecular weight]]
+|bgcolor="#dfefff"|1202.61
+|-
+|bgcolor="#efefef"|Bioavailability
+|bgcolor="#dfefff"|?
+|-
+|bgcolor="#efefef"|Metabolism
+|bgcolor="#dfefff"|[[Liver]]
+|-
+|bgcolor="#efefef"|[[half life|Elimination half life]]
+|bgcolor="#dfefff"|19 hours
+|-
+|bgcolor="#efefef"|[[Excretion]]
+|bgcolor="#dfefff"|Bile
+|-
+|bgcolor="#efefef"|[[ATC code]]
+|bgcolor="#dfefff"|L04AA01
+|-
+|bgcolor="#efefef"|[[Pregnancy category (pharmaceutical) | Pregnancy category]]
+|bgcolor="#dfefff"|C ([[United States|USA]]) <br /> C ([[Australia|Aus]])
+|}
 '''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 [[Transplant_rejection|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 [[corticosteroid]]s.
-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 drug is sold by [[Novartis]] under the brand names '''Sandimmune'''® and '''Neoral'''®. Generic cyclosporine drugs have been produced by companies such as [[Sangstat]], [[Abbott Laboratories]] and [[Gengraf]]. Annual sales of cyclosporine are around $1 billion.
 Cyclosporine is thought to bind to the cytosolic protein Cyclophylin (Immunophylin)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 IL-2. It also inhibits lymphokine production and [[interleukin]] release and therefore leads to a reduced function of effector T-cells. It does not effect cytostatic activity.
@@ Line 9: / Line 37: @@
 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 acid]]s. The chemical name of cyclosporine is [R-[R<font size = "-1"><sup>*</sup></font>,R<font size= "-1"><sup>*</sup></font>-(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-&alpha;-amino-butyryl-''N''-methylglycyl-''N''-metyl-L-leucyl-L-valyl-''N''-methyl-L-leucyl) and the empirical formula is C<font size= "-1"><sub>62</sub></font>H<font size= "-1"><sub>111</sub></font>N<font size= "-1"><sub>11</sub></font>O<font size= "-1"><sub>12</sub></font>.
+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 acid]]s. The chemical name of cyclosporine is [R-[R<font size = "-1"><sup>*</sup></font>,R<font size= "-1"><sup>*</sup></font>-(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-&alpha;-amino-butyryl-''N''-methylglycyl-''N''-methyl-L-leucyl-L-valyl-''N''-methyl-L-leucyl) and the empirical formula is C<font size= "-1"><sub>62</sub></font>H<font size= "-1"><sub>111</sub></font>N<font size= "-1"><sub>11</sub></font>O<font size= "-1"><sub>12</sub></font>.
 Compare with [[tacrolimus]].