Limited sampling strategies for estimating cyclosporin area under the concentration-time curve: Review of current algorithms

Cyclosporin, the drug of first choice in transplantation surgery, is characterized by a low therapeutic index and variable absorption, so close monitoring of the drug is required to optimize the dosing. Predose blood cyclosporin levels are measured routinely for therapeutic monitoring, but this approach is not optimal because the area under the concentration-time curve (AUC) correlates better with clinical events. However, conventional methods of measuring AUC require many blood samples, which is not viable in a routine clinical setting. AUC monitoring can be simplified for use in a clinical setting by using a limited sampling strategy (LSS) that allows AUC to be estimated using a small number of blood samples collected at specific times. This article reviews the current literature on estimating cyclosporin AUC using LSS. Thirty-eight papers suggesting the use of specific time points were found. LSS has been developed for different transplant types, with different dosing regimens, and with different assays. Most authors suggested either two- or three-sample equations. Results from authors who validated their models suggest that equations defined on one transplant type may be applicable to other transplant types, to both adults and children, and to early or late after transplantation. Moreover, it seems that there is flexibility in the choice of equations available to clinicians. The number of samples to collect for accurate estimations is a matter of debate, but a wise choice can minimize the number. The choice of the optimal LSS and validation are discussed.