Clinical Information

Cyclosporine is a lipophilic polypeptide used to prevent rejection after solid organ transplantation; it suppresses T-cell activation by inhibiting calcineurin to decrease interleukin-2 (IL-2) production. There is substantial interpatient variability in absorption, half-life, and other pharmacokinetic parameters. Cyclosporine is extensively metabolized by cytochrome P450 (CYP) 3A4 to at least 30 less-active metabolites, many of which are detected by immunoassays. Cyclosporine is known for many drug interactions, including increased neuro- and nephrotoxicity when coadministered with antibiotics, antifungals, or other immunosuppressants. Cyclosporine has a narrow therapeutic range with frequent adverse effects making therapeutic drug monitoring essential.

With 80% of cyclosporine sequestered in erythrocytes, whole blood is the preferred specimen for analysis. Dose is adjusted initially (up to 2 months posttransplant) to maintain concentrations generally between 150 and 400 ng/mL. Target trough concentrations vary according to clinical protocol and depend on type of allograft, risk of rejection, concomitant immunosuppressive drugs, and toxicity. After the first 2 postoperative months, the target range is generally lower, between 75 and 300 ng/mL. Conversion between formulations is generally done at the same dose but with drug monitoring.