Methods for Clinical Monitoring of Cyclosporin in Transplant Patients

Cyclosporin was introduced into clinical practice in the early 1980s and has since been shown to prolong survival for transplant recipients. Because cyclosporin is a narrow therapeutic index drug and there are significant consequences associated with ‘subtherapeutic’ and ‘supratherapeutic’ concentrations, cyclosporin therapy is monitored as part of routine patient follow-up. However, the optimal method for the therapeutic drug monitoring of cyclosporin has yet to be defined. Currently, the most common method involves monitoring pre-dose trough concentrations, but this method is less than ideal.

Other methods of monitoring cyclosporin therapy include monitoring the area under the concentration-time curve, limited sampling strategies, monitoring of single concentrations other than troughs and pharmacodynamic monitoring. Bayesian forecasting has been used successfully in clinical practice with other drugs with narrow therapeutic indices. However, few studies are available regarding Bayesian forecasting and cyclosporin. Existing studies are preliminary in nature and involve the old Sandimmun® formulation rather than the Neoral® formulation. Although these methods show promise, they have not gained widespread acceptance. This is because of their impracticality and the lack of prospective studies comparing other monitoring methods with trough concentration monitoring. Further comparative studies evaluating the impact of the specific monitoring method on definite patient outcomes are warranted.