THERAPEUTIC MONITORING FOR CYCLOSPORINE - DIFFICULTIES IN ESTABLISHING A THERAPEUTIC WINDOW

Despite the fact that cyclosporine (CsA) has been used clinically for a number of years, there is still uncertainty about the efficacy of monitoring its blood levels. Few if any studies have documented clear differentiation of rejection, immunosuppression, and toxicity on the basis of CsA concentrations alone. The issues in CsA monitoring include selection of sample matrix, analytical method, dosing interval and the timing of trough measurements, the temporal relationship between measurements and physiological events such as toxicity, the concurrent presence of multiple other immunosuppressive agents, and the lack of "gold standards" for determining rejection, adequate immunosuppression, and toxicity. In contrast to using CsA levels for the differential diagnosis of rejection and toxicity, there is evidence that maintenance of CsA concentrations within a therapeutic window results in a lower prevalence of toxicity and rejection.