Abstract:
Introduction. Tacrolimus, the calcineurin inhibitor has been the cornerstone of immunosuppression
following renal transplantation for the last 10–15 years. The narrow therapeutic index and large
pharmacokinetic interindividual and intraindividual variability makes therapeutic drug monitoring
(TDM) of tacrolimus mandatory. The purpose of the study was to focus on tacrolimus
pharmacokinetics, pharmacodynamics, and toxicity profiles to highlight the importance of TDM for
post-transplant management.
Material and methods. A narrative literature search was performed in the Hinari database with source
selection for the last 5 years. Keywords used for the search were: tacrolimus pharmacokinetics, TDM
of tacrolimus, tacrolimus in renal transplantation. Inclusion criteria were: clinical trials, literature
reviews accessible in full-text, articles published in English. Exclusion criteria were: articles without
full-text version, studies with irrelevant results, case reports, letters to the editor or articles in languages
other than English. Out of 129 articles found, 39 articles were included in the study after reviewing the
title, abstract, inclusion and exclusion criteria.
Results: Therapeutic doses of tacrolimus are adjusted by monitoring the morning whole blood trough
concentrations. Achieving trough levels of 7–12 ng/mL (preferably to > 7 ng/ml, following the second
consensus report in 2019) early post-transplant reduces the risk of acute rejection compared to trough
levels of 4–7 ng/mL (2009 European consensus conference), while levels between 5.35 and 7.15 ng/mL
manage to balance acute rejection prevention and infection risk. These data highlight the importance
of personalized therapeutic drug monitoring (TDM) for optimal transplant outcomes. Pharmacokinetic
variability of tacrolimus may be caused by variable absorption, low bioavailability, increased risk of
drug interactions, liver and renal function, genetic polymorphisms. The side effects of tacrolimusnephrotoxicity, neurotoxicity, cardiotoxicity, metabolic disturbances, infections can be prevented by
monitoring and adjusting the dose as needed.
Conclusion. Tacrolimus is essential immunosuppressive agents for preventing organ rejection in
kidney transplant patients, but its use is associated with significant variability in response that requires
careful management, including TDM and pharmacogenomics, avoiding drug interactions, proper
dosage regimen. Therapeutic drug monitoring guides healthcare providers to achieve therapeutic
efficacy (prevention of graft rejection), and limit potential dose-dependent toxicities.
