Cyclosporine, Whole Blood, Immunoassay

Use

Cyclosporine is an immunosuppressive agent derived from Tolypocladium inflatum gams, a fungus originally isolated from a Norwegian soil sample. The agent is used extensively to control rejection of organ transplants, especially of liver, heart, or kidney. The effectiveness of cyclosporine results from specific and reversible inhibition of immunocomponent lymphocytes in the G0 and G1 phase of the cell cycle. T-lymphocytes are preferentially inhibited. The T-helper cell is the main target, although the T-suppressor cell may also be suppressed. Cyclosporine also inhibits lymphokine production and release including interleukin-2. Monitoring of blood levels is imperative because the pharmacokinetics of cyclosporine are not only complex, but vary over time in the same patient; thus, blood levels cannot be well predicted from dosing schedules. Furthermore, this drug has a narrow therapeutic window, and significant toxicity at levels above that range. Renal toxicity with eventual renal failure is the most severe complication. Other assays used to assess renal function (ie, BUN, creatinine clearance) should be ordered along with cyclosporine level, since toxicity may begin even with "acceptable" blood levels. Other toxicity includes hypertension, convulsions, tremors, pulmonary edema, and an increased risk of lymphoma. Drugs that enhance the potential toxicity of cyclosporine, include aminoglycoside antibiotics, amphotericin B, acyclovir, ketoconazole, lovastatin, NSAIDS, and ranitidine.