Clinical use
Cyclosporin is a cyclic undecapeptide of fungal origin and a potent immunosuppressive agent. The introduction of cyclosporin in human kidney transplantation in the late 1970s was a major step forward in transplantation medicine, and substantially improved patient and graft survival in patients receiving heart, kidney, liver, pancreas, lung or bone marrow transplants. The use of cyclosporin is also associated with renal dysfunction, tremor, hirsutism, hypertension, and gum hyperplasia. The application of therapeutic drug monitoring (TDM) and concentration-controlled dosing in order to maintain each patient’s drug exposure within a narrow therapeutic window can be achieved by measurement of pre-dose (trough level) cyclosporine concentrations.
Background
Cyclosporin was the first drug identified to specifically and reversibly inhibit the activation and proliferation of lymphocytes and represents the prototype of the drug class of calcineurin inhibitors. The main mechanism through which cyclosporin exerts its immunosuppressive effect is believed to be via the inhibition of T cell activation and proliferation. Intracellular cyclosporin binds to both cyclophilin A and B and these complexes then inhibit the enzymatic activity of calcineurin. This inhibition restricts the dephosphorylation and nuclear translocation of nuclear factor of activated T cells, which regulates transcription of several cytokines, including IL‑2, IL‑4, TNF‑α, and interferon‑γ, and therefore limits lymphocyte activation and proliferation.
Reference range
No firm therapeutic range exists for cyclosporin. The patient’s clinical state, individual differences in sensitivity to immunosuppressive and nephrotoxic effects of cyclosporin, coadministration of other immunosuppressants, type of transplant, time post-transplant, and other factors contribute to different requirements for optimal blood levels of cyclosporin. Individual cyclosporin values cannot be used as the sole indicator for making changes in the treatment regimen. Each patient should be thoroughly evaluated clinically before treatment adjustments are made.
Specimen requirements
EDTA (purple top) specimen. The specimen should be collected just before the next dose of tacrolimus is to be taken ie. trough level.
Turnaround time
Two batches of cyclosporine are analysed each working week (Tuesday and Friday, as agreed with renal medicine) so that the maximum turnaround time for a specimen is 3 to 4 days.