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Calcineurin inhibitors (CNIs) are maintenance immunosuppressive drugs that have been used as the main therapy for organ transplantation for many years. Of the CNIs, cyclosporine (CYA) and tacrolimus (TAC) are used in clinical practice. The CYA binding protein is cyclophilin and that of TAC is FK-binding protein (FKBP), but both drugs have same mechanism of action: the inhibition of interleukin 2 (IL-2) production by binding the binding protein complex to calcineurin (CN). It is thought that the area under the concentration time curve (AUC) for both drugs may be the pharmacokinetic (PK) parameter that is the most associated with clinical effect. However, oral CYA administration gave a blood concentration–time curve with a high CYA peak concentration (Cp), and oral TAC showed a gradual blood concentration–time curve, keeping at the minimum of the therapeutic range; both drugs vary significantly in their pharmacokinetics1). The Cp of CYA has increased since the Neoral® preparation of CYA was used, compared with Sandimmune®, whereas the Cp of TAC decreased since using a sustained release preparation; thus the differences between CYA and TAC are considerable2). Although the optimal pharmacokinetics of both drugs may be similar to those of other drugs with the same mechanism of action, no conclusions have been reached on whether the peak blood concentration, or a specific maintained blood concentration, is required for CNI pharmacokinetics, even if both drugs show identical AUCs. In addition, although CYA and TAC are similar CNI drugs, there are differences in the recommended monitoring points of CYA and TAC; these points are the C2 level (the blood concentration 2 h after oral administration), which mainly reflects Cp, and the trough concentration (Ct)3-8), respectively911). To solve these problems, it is necessary to consider comprehensively not only AUC, but also Cp, Ct, and time above the minimum effective concentration (%T > MEC). We discuss the optimal pharmacokinetics of CNIs by comparing various aspects of CYA and TAC.

Optimal Pharmacokinetics of Cyclosporine and Tacrolimus Based Relationship Among AUC, Trough and Peak Concentration