Measuring Intracellular Concentrations of Calcineurin Inhibitors: Expert Consensus from the International Association of Therapeutic Drug Monitoring and Clinical Toxicology (IATDMCT) Expert Panel

Therapeutic drug monitoring (TDM) of the two calcineurin inhibitors (CNIs), tacrolimus (TAC) and cyclosporine A (CsA), has resulted in improvements in the management of patients who have undergone solid organ transplantation. As a result of TDM, acute rejection rates and treatment-related toxicities have been reduced. Irrespective, acute rejection and toxicity still occur in patients who have undergone transplantation showing blood CNI concentrations within the therapeutic range. Moreover, the acute rejection rate is no longer decreasing. Hence, smarter TDM approaches are necessary. As CNIs exert their action inside T-lymphocytes, intracellular CNIs may be a promising candidate for improving therapeutic outcomes. Intracellular CNI concentration may be more directly related to drug effect and has been favorably compared with the standard, whole-blood TDM for TAC in liver transplant recipients. However, measuring intracellular CNIs concentrations is not without pitfalls at both the pre-analytical and analytical stages, and standardization appears essential in this area. To date, there are no guidelines for the TDM of intracellular CNI concentrations.