Intra-patient variability in tacrolimus exposure: causes, consequences for clinical management

Tacrolimus (Tac) is widely used for the prevention of rejection after solid organ transplantation. Finding the optimal balance between effective Tac concentrations and toxicity is a challenge and requires therapeutic drug monitoring. In addition to the well-known inter-patient variability, the clinical use of Tac is also complicated by considerable intra-patient variability (IPV) in Tac exposure. Tac IPV is defined as the amount of fluctuation of whole-blood concentrations over a certain period of time during which the Tac dose remains unchanged. A high IPV in Tac exposure has recently been recognized as a strong risk factor for acute rejection and poor long-term kidney transplantation outcome. In addition to non-adherence, several other factors determine the magnitude of the IPV in Tac exposure. Quantification of IPV is easy and can be easily incorporated into everyday clinical practice as a tool for optimizing transplantation outcomes.