Definition
- Cyclosporin A is a cyclic polypeptide containing 11 amino acids. It is produced by the fungus Tolypocladium inflatum.
- Sirolimus is a macrocyclic triene antibiotic that is produced by fermentation of Streptomyces hygroscopicus. Sirolimus was discovered from a soil sample collected in Rapa Nui, which is also known as Easter Island. Structurally, sirolimus resembles tacrolimus and binds to the same intracellular binding protein or immunophilin known as FKBP-12.
- Tacrolimus is a macrolide antibiotic produced by Streptomyces tsukubaensis.
- Other names: cyclosporine (Sandimmune, Neoral); sirolimus (Rapamycin, Rapamune), and tacrolimus (FK-506, Prograf).
- Normal range: see Table 16.46.
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TABLE 16 " “46Normal Ranges of Immunosuppressants Following TransplantationView LargeTABLE 16 " “46Normal Ranges of Immunosuppressants Following Transplantation Drug Type of Transplant Therapeutic Concentration (ng/mL) 12 h Postdose Cyclosporin A Renal 100 " “200 Cardiac 150 " “250 Hepatic 100 " “400 Bone marrow 100 " “300 Toxicity at >400 Sirolimus 4 " “20 (trough) Kidney 4 " “12 Liver 12 " “20 Tacrolimus 5 " “20 (12-h trough level) Kidney and liver 0 " “2 mo posttransplant 10.0 " “15.0 3 mo and older 5.0 " “10.0 Heart 0 " “2 mo posttransplant 10.0 " “18.0 3 mo and older 8.0 " “15.0 Toxicity at ≥26
Use
- Cyclosporine is a drug that suppresses the immune system and is used to prevent organ rejection and marrow transplant. It is used in combination with other immunosuppressants or corticosteroids.
- Although sirolimus was originally developed as an antifungal agent, it was later found to have immunosuppressive and antiproliferative properties.
- Tacrolimus is an immunosuppressive drug that has been shown to be effective for the treatment of rejection following transplantation. Tacrolimus has been used for therapy of the following disorders: adult RA, as a single agent or in combination with methotrexate, adult refractory myositis, systemic sclerosis, Crohn disease, autoimmune chronic hepatitis, pediatric autoimmune enteropathy, uveitis, steroid-resistant nephrotic syndrome (severe), recalcitrant chronic plaque psoriasis, and atopic dermatitis (administered as ointment).
Limitations
- Testing performed on whole-blood samples.
- Clotted and/or frozen specimens unacceptable.
- Testing performed by immunoassay or LC/MSn (multiple MS) technology.
- Immunoassay (e.g., MEIA, EMIT, FPIA, RIA): FPIA demonstrates more cross-reactivity with cyclosporine metabolites than EMIT. Therefore, EMIT concentration may be 70% of FPIA concentration. Note that cross-reactivity of immunoassays may change over time, so consult the manufacturers package insert for current information.
- LC/MS concentrations are generally lower than immunoassay due to cross-reactivity of the immunoassay with metabolites.