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cyclosporin is a lipophilic cyclic polypeptide isolated from a
fungus: tolypocladium inflatum, cylindrocarpon lucidium.
It was discovered in 1972.
Though the years it has been used in several conditions.
These include
Psoriasis,
Behcets's disease,
Inflammatory bowel disease, and
Rheumatoid arthritis.
It has also made a major impact in transplantation surgery.
It is poorly absorbed into
the body and enters this cell where it binds to intra cellular protein
cyclophilin. It
forms a complex calcineurin in the cell. It inhibits the phosphatase activity of
calcineurin, and prevents the transcription of mRNA for IL-2 and other cytokines.
As a result there is a blockade of T-cell activation and stimulation.
cyclosporin is metabolized in the liver and 90 percent is
eliminated in the bile.
Six percent is eliminated in the kidney.
A microemulsified form is available as neoral.
This results in a better absorption of the drug.
Because the drug is metabolized in the liver, it is subject to
many drug interactions.
The level or cyclosporin is increased by many drugs which compete with the c-p450 liver
enzyme.
These include :
ketoconazole,
Calcium antagonists,
H-2 antagonists, and
some antibiotics, especially erythromycin.
In addition, caution is required in
renal disease or dysfunction.
Drugs that cause renal toxicity, especially aminoglycosides, and nonsteroidal
Anti-inflammatory drugs, should also be used with caution.
Many trials have been done in rheumatoid arthritis, that show
good efficacy.
Combination with methotrexate has also been shown to boost efficacy in those patients who
have not responded well to methotrexate alone.
Studies suggest that an increase in dose of the cyclosporin, results in a greater renal
toxicity but a better efficacy.
Studies have been performed using doses between 2.5 mg/kg and 10 mg/kg.
Most sources recommend starting dose of 2.5 mg/kg increasing by one mg/kg per week with a
maximum dose of 5 mg/kg.
If it is important to monitor serum creatinine, liver enzymes, serum potassium.
Monitoring should be done 2 weekly for the first three months,
and then monthly thereafter.
Prior to therapy it is important to exclude :
Known or previous
malignancy,
Patients with poorly controlled blood pressure, or
Renal disease or dysfunction.
Caution should also be taken in liver dysfunction.
It is likely that response to therapy will be seen within 2
months.
It is no response by six months, then it is unlikely that improvement will be seen and the
drug should be stopped.
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on-line.