Therapeutic monitoring of cyclosporine.

Therapeutic monitoring of immunosuppressive therapy with cyclosporine is a critical requirement because of intra- and interpatient variability of drug absorption, narrow therapeutic window and drug induced nephrotoxicity. The most widely used procedure involves measuring trough concentrations of cyclosporine (CsA) parent drug in whole blood using a specific monoclonal immunoassay. Trough concentrations generally correlate with adverse clinical events, e.g., episodes of rejection and nephrotoxicity. However, they do not correlate consistently with chronic events to allow prediction of adverse outcome. There is now increasing interest in using CsA pharmacokinetic profiling as a means of monitoring. This approach appears to offer a more valid index of drug exposure and hence a better prediction of clinical outcome. Nevertheless, multiple blood sample requirement and the complexity of pharmacokinetic profiling impose practical concern. The overall merit of either approach awaits further studies comparing clinical efficacy, technical requirements, and economic issues.