Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
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 CYP3A4 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.
Monitoring whole blood cyclosporine concentration during therapy, particularly in individuals coadministered CYP3A4 substrates, inhibitors, or inducers
Adjusting dose to optimize immunosuppression while minimizing toxicity
Evaluating patient compliance
Most individuals display optimal response to cyclosporine with trough whole blood levels 100 to 400 ng/mL. Preferred therapeutic ranges may vary by transplant type, protocol, and comedications. Therapeutic ranges are based on specimens drawn at trough (ie, immediately before the next scheduled dose). Blood drawn at other times will yield higher results. This test may also be used to analyze cyclosporine levels 2 hours after dosing (C2 concentrations); trough therapeutic ranges do not apply to C2 specimens.
The assay is specific for cyclosporine; it does not cross-react with cyclosporine metabolites, sirolimus, sirolimus metabolites, tacrolimus, or tacrolimus metabolites. Results by liquid chromatography with detection by tandem mass spectrometry are approximately 30% less than by immunoassay.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
The recommended therapeutic ranges described above apply to trough specimens drawn just before a dose. Blood drawn at other times will yield higher results.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
100-400 ng/mL (Trough)
Target steady-state trough concentrations vary depending on the type of transplant, concomitant immunosuppression, clinical/institutional protocols, and time post-transplant. Results should be interpreted in conjunction with this clinical information and any physical signs/symptoms of rejection/toxicity.
Clinical References Provides recommendations for further in-depth reading of a clinical nature
1. Moyer TP, Post GR, Sterioff S, et al: Cyclosporine nephrotoxicity is minimized by adjusting dosage on the basis of drug concentration in blood. Mayo Clin Proc 1988 March;63(3):241-247
2. Kahan BD, Keown P, Levy GA, et al: Therapeutic drug monitoring of immunosuppressant drugs in clinical practice. Clin Ther 2002 March; 24(3):330-350
3. Dunn CJ, Wagstaff AJ, Perry CM, et al: Cyclosporin: an updated review of the pharmacokinetic properties, clinical efficacy, and tolerability of a microemulsion-based formulation (Neoral) 1 in organ transplantation. Drugs 2001;61(13):1957-2016