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Cyclosporine

Cyclosporine is a powerful immunosuppressant that is given to organ transplant recipients to minimize rejection. Oral absorption is about 40% and plasma levels peak in 2 to 4 hours. Oral availability is highly variable, ranging from 10 to 70% due to incomplete absorption from the gut. A new formulation of cyclosporine, Neoral, has better absorption and more consistent blood levels. Cyclosporine is metabolized predominantly in the liver by the hepatic cytochrome P-450 system and the metabolites are eliminated in the bile. Less than 3% of the parent drug is eliminated in the urine. The circulating half life is 8 to 24 hours and may be prolonged in patients with liver, but not renal, disease.

Optimal dosing is difficult because absorption, distribution, metabolism, and excretion vary widely, and are affected by altered gastrointestinal and liver function. Dosages must be individualized to maintain cyclosporine levels within a narrow therapeutic window. Low doses do not adequately suppress the immune system, while high doses produce toxic effects such as renal failure and hyperkalemia. Cyclosporine also has significant interactions with other drugs frequently given to transplant recipients.

The therapeutic range performed by fluorescence polarization immunoassay is:

Transplant

Therapeutic Range (ng/mL)

Cardiac <3 months postop

150 – 300

Cardiac >3 months postop

30 – 150

Renal

100 - 400

Bone marrow

200 – 500

In addition to cyclosporine trough levels, other laboratory parameters should also be followed including; CBC, serum electrolytes, BUN, creatinine, magnesium, and urinalysis.

Specimen requirement is one 5 mL lavender top (EDTA) tube of blood.

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