New Approaches to Cyclosporine Monitoring Raise Further Concerns about Analytical Techniques

Of late there has been a re-evaluation of therapeutic drug monitoring (TDM) strategies for optimizing cyclosporine (CsA) dosing in organ transplant recipients. Following the widespread introduction of the microemulsion formulation of CsA (Neoral®; Novartis Pharma), there has been a renewed interest in approaches to TDM that are based on the original observations of Lindholm and Kahan (1). These authors demonstrated that total exposure to CsA, as reflected by the area under the concentration-time curve (AUC), was a better predictor of outcomes than predose (trough) CsA concentrations. Furthermore, several studies have shown that the AUC can be estimated with good reliability by means of a limited sampling strategy (2)(3)(4). Recently, clinical studies utilizing CsA measurements made at single or multiple time points in the early period (0–6 h) after CsA ingestion have shown the potential of such measurements for improving clinical outcomes compared with the traditional, predose, approach (5)(6)(7). These studies have made recommendations for target CsA concentration ranges at either specific postdose time points (2 or 3 h) or for limited AUC measurements in the period 0–6 h post dose. The recommendations were based on particular immunoassay methods and were for either kidney or liver transplant patients. We would like to raise two issues that may require further investigation before these new target CsA concentrations are adopted by other centers.