Therapeutic Drug Monitoring of Cyclosporin

Abstract

Cyclosporin, a potent immunosuppressive agent used to prevent rejection of transplanted organs, has a narrow therapeutic range and various toxic effects, mostly concentration-dependent. The kinetics of this drug present a large intra- and interindividual variability due to many factors resulting in marked variations of blood cyclosporin concentrations, and in a poor correlation between administered dose and concentrations. The knowledge of cyclosporin peculiarities and of factors affecting blood concentrations can provide a rational basis for establishing an adequate therapy for the individual patient, in conjunction with other laboratory and clinical data. Cyclosporin monitoring is a method of evaluating whether the therapeutic choice is correct. Cyclosporin concentrations can be measured in blood, plasma and serum using radioimmunoassay or high performance liquid chromatography. Different results are obtained, depending on the technique and on biological fluids used. Cyclosporin measurement presents many problems and difficulties. There is a need for standardisation and for quality assessment programmes. The recent development of monoclonal antibodies may represent a significant advance for cyclosporin monitoring. The most important factors affecting blood concentrations are: type of transplant, bile deficit, gastrointestinal dysfunction, food, variations of lipoprotein concentrations, impairment of liver function, age, drug coadministration. Therapeutic drug monitoring should be undertaken on a regular basis after the initiation of therapy with cyclosporin. After discharge from the hospital the patient and the attending physician should be aware of the factors which may require changes in cyclosporin therapy.