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Review
. 2023 Aug 21:2:1160752.
doi: 10.3389/frtra.2023.1160752. eCollection 2023.

Tacrolimus-why pharmacokinetics matter in the clinic

Lino Henkel  1 , Ulrich Jehn  1 , Gerold Thölking  1   2 , Stefan Reuter  1
Affiliations
Review

Tacrolimus-why pharmacokinetics matter in the clinic

Lino Henkel et al. Front Transplant. .

Abstract

The calcineurin inhibitor (CNI) Tacrolimus (Tac) is the most prescribed immunosuppressant drug after solid organ transplantation. After renal transplantation (RTx) approximately 95% of recipients are discharged with a Tac-based immunosuppressive regime. Despite the high immunosuppressive efficacy, its adverse effects, narrow therapeutic window and high intra- and interpatient variability (IPV) in pharmacokinetics require therapeutic drug monitoring (TDM), which makes treatment with Tac a major challenge for physicians. The C/D ratio (full blood trough level normalized by daily dose) is able to classify patients receiving Tac into two major metabolism groups, which were significantly associated with the clinical outcomes of patients after renal or liver transplantation. Therefore, the C/D ratio is a simple but effective tool to identify patients at risk of an unfavorable outcome. This review highlights the challenges of Tac-based immunosuppressive therapy faced by transplant physicians in their daily routine, the underlying causes and pharmacokinetics (including genetics, interactions, and differences between available Tac formulations), and the latest data on potential solutions to optimize treatment of high-risk patients.

Keywords: kidney transplantation; renal transplantation; tacrolimus; tacrolimus formulation; tacrolimus metabolism; tacrolimus pharmacokinetics.

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Conflict of interest statement

SR and GT received travel support and lecture fees from Chiesi. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author SR declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

Figures

Figure 1
Figure 1
Schematic visualizations of the pharmacokinetics of different tacrolimus formulations. ER-Tac, extended-release tacrolimus, Advagraf®; IR-Tac, immediate-release tacrolimus, Prograf®; LCP-Tac, once-daily, Envarsus®, arrows mark the different peak concentrations.
Figure 2
Figure 2
Flow chart for practical identification of fast metabolizers.
See this image and copyright information in PMC

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