Klin Farmakol Farm. 2009;23(4):187-193

Cyclosporin A: pharmacokinetics, monitoring and use of rheumatology

David Suchý¹, Milan Grundmann²

¹ Oddělení klinické farmakologie FN Plzeň

² Ústav klinické farmakologie, FN Ostrava a Fakulta zdravotnických studií, Ostravská univerzita, Ostrava

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.

Keywords: cyclosporin, mechanism of action, pharmacokinetics, therapeutic drug monitoring, autoimmune disorders

Published: May 1, 2010  Show citation