Intracellular Concentrations of Immunosuppressants

Although therapeutic drug monitoring has been standard of care in immunosuppressive therapy for quite a while, acute rejections remain a significant problem, particularly immediately following transplantation and despite trough whole blood concentrations within the therapeutic range. The widely used calcineurin inhibitors exert their effect inside the lymphocyte, where they bind to specific proteins, thus interfering with T-cell activation. This makes the intracellular compartment of peripheral blood mononuclear cells an attractive target for concentration monitoring of calcineurin inhibitors. A number of papers have shown that there is no or only a weak correlation between intracellular concentrations of calcineurin inhibitors and their whole blood trough concentrations, which are currently regularly monitored. However, it has also been reported that such measurements that have become feasible through advances in analytics, such as the widespread introduction of liquid chromatography combined with tandem mass spectrometry, have the potential to better predict clinical outcomes than is possible with conventional whole blood monitoring. However, these results are still early, and more work needs to be done in this field.