The significance of determining the therapeutic dose of cyclosporine-A in patients undergoing organ transplantation

Abstract

Immunosuppressive drugs are now unavoidibly used after the transpantation of liver,heart and bone marrow, as well as in certain autoimmune diseases.among these agents,cyclosporine-A (CYA) is one of the most effective Immunosuppressants which is widely used.but as any Immunosuppressive agent,the use of CYA is not without harmful side effects.neurotoxin,nephrotoxic and hepatotoxic complications,may be seen in patients treated with CYA. for the first time borel from sandoz research center (Switzerland) showed that the metabolite of a fungus named tolypcladium inflatum gams,has a suppressive effect on immune system.thirty intermediate products of CYA metabolic pathway have been known so far and some studies have demonstrated the properties of a limited number of these products (M1,M8,M17,M21).pharmacodynamic studies on CYA have revaled that the Immunosuppressive effect of this drug is mainly achievable by its activity on T-lymphocyte.in fact.CYA inhibits the gene transcription in T-lymphocytes which results in lesser or no production of antigen-antibody complex.since the administred therapeutic dose of drug is a variable of many factors such as the type of transplanted organ,physiologic state of the patient,bioavailability and the treatment protocol and on the other hand,CYA has some destructive side effects on the other body organs,therefore determinations of the effective therapeutic dose of CYA ,and freauent measurement of CYA and its metabolites concentrations in blood is a necessity.