Cyclosporine is a cyclic undecapeptide of fungal origin and a potent immunosuppressant. It is used as a primary agent during immunosuppressive therapy for solid organ transplants. Immunosuppression is thought to be the result of impairment of T-cell receptor transcription of the IL-2 gene. Cyclosporine therapy has greatly improved organ transplant survival of heart, liver and kidney transplants. Cyclosporine may be administered by IV or orally. Absorption from the gastrointestinal tract is variable, unpredictable, and incomplete. Bioavailability increases during treatment so oral doses must be gradually reduced in order to maintain a constant cyclosporine concentration in the blood. Assessment of cyclosporine concentrations in blood aids in adjusting patients’ dosage and avoids cyclosporine underdosage inefficacy or overdosage toxicity. Cyclosporine is eliminated almost completely by hepatic metabolism; cytochrome P-450 enzymes being responsible for
the biotransformation of cyclosporine and its metabolites. More than thirty metabolites have been identified.
Preliminary data indicate cyclosporine metabolites are less immunosuppressive and less toxic than their parent compound. The use of cyclosporine is associated with serious toxic side effects, primarily nephrotoxicity and hepatotoxicity Other adverse effects include diarrhea, gum hyperplasia, nausea, vomiting, hirsutism, tremor, and hypertension. Some studies have shown the benefits of monitoring cyclosporine concentrations, including a reduction in the incidence of biopsy proven acute rejection.