Klin Farmakol Farm. 2009;23(4):187-193
Cyclosporin–A (CSA) is a cyclic polypeptide with immunosupressant properties. The main use of cyclosporine is immunosuppression for
solid organ transplantation, but also in graft versus host disease, bone marrow transplantation and variety of autoimmune disorders
eg. rheumatoid artrhrtitis, systemic lupus, psoriasis). Cyclosporin is a specific T-lymfocyte suppressor, primarily acting on T helper cells,
with a unique effect on the primary immune response. Its inhibits production of interleukin -2 (IL-2) and other cykokines by activated
lymphocytes. Cyclosporin has low water solubility, and its gastrointestinal absorption can be influenced by many variables. Microemulsion
version of cyclosporine was marketed to help reduce absorption variability.
Cyclosporin is almost completely eliminated by hepatic metabolism, mainly via the the cytochrome P450-depend mono-oxygenase
system (P450s), subfamily P450 3A4
(P450 3A4, 3A5, and newly discovered 3A43). There is no doubt that the P450s has the great effect on interindividual variability of drug
response. The most active metabolites AM1, followed by AM9, display 10–20 % of the immunosuppressive activity of cyclosporin. Monitoring
of immunosuppressant therapy in transplantology is common, cyclosporin is assayed by radioimmunoassay (RIA) or high pressure
lipid chromatography (HPLC) or newly liquid chromatography-mass spectrometry (LCMS/MS.)
Authors describes cyclosporin basic pharmacokinetic, therapeutic drug monitoring (TDM) strategies and its use in autoimmune disorders.
Published: May 1, 2010 Show citation