Abstract
Background and objective
Tacrolimus is a cornerstone of immunosuppression after kidney transplantation; however, its narrow therapeutic window and substantial inter- and intra-individual pharmacokinetic variability complicate dose optimization. Extended-release tacrolimus (ER-Tac) and MeltDose® prolonged-release tacrolimus (LCP-Tac) formulations have been developed to improve bioavailability and stabilize drug exposure. The concentration-to-dose (C/D) ratio has emerged as a clinically relevant surrogate marker of tacrolimus metabolism and apparent clearance. We aimed to evaluate long-term differences in C/D ratio dynamics between once-daily tacrolimus formulations.Methods
In this single-center retrospective study, 100 de novo kidney transplant recipients (2015-2018) received either ER-Tac (n = 50) or LCP-Tac (n = 50). Tacrolimus trough concentrations, daily doses, and laboratory parameters were collected up to 60 months post-transplantation. Longitudinal pharmacokinetic assessment was performed using repeated C/D ratio measurements. Linear mixed-effects models adjusted for recipient age and time post-transplantation were used for analysis. Clinical outcomes included delayed graft function (DGF), biopsy-proven acute rejection (BPAR), new-onset diabetes after transplantation (NODAT), and mortality.Results
LCP-Tac-treated patients required significantly lower daily doses from month 3 onward (p Conclusion
LCP-Tac was associated with lower dose requirements and higher, more stable C/D ratios compared with ER-Tac, suggesting formulation-dependent differences in tacrolimus pharmacokinetics. The C/D ratio may serve as a simple, clinically applicable surrogate marker for long-term pharmacokinetic monitoring in kidney transplant recipients.