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Tacrolimus, a calcineurin inhibitor, is widely used for prophylaxis because it suppresses T-cell activation. However, its clinical use is complicated by a narrow therapeutic window and marked pharmacokinetic variability. Therapeutic drug monitoring based on trough whole-blood concentrations is routinely used to guide dosing, but this approach has limitations, particularly in transplantation recipients who experience rapid physiological and hematological changes. This review summarizes recent insights into determinants of tacrolimus pharmacology in hematopoietic stem cell transplantation and discusses emerging perspectives for individualized dosing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Main body<\/jats:title>\n                    <jats:p>Tacrolimus exerts its immunosuppressive effects by forming a complex with FK506-binding proteins that inhibits calcineurin and suppresses activation of nuclear factor of activated T cells. Beyond this canonical mechanism, interactions with FK506-binding proteins influence the distribution of tacrolimus within blood cells. Because tacrolimus strongly divides into erythrocytes and leukocytes, whole-blood concentrations reflect systemic exposure and drug binding within circulating blood components. In recipients of hematopoietic stem cell transplantation, marked fluctuations in blood cell counts during conditioning therapy and hematopoietic recovery can alter this distribution, potentially causing changes in concentrations without corresponding changes in pharmacologically active exposure. Genetic variation in drug-metabolizing enzymes further contributes to variability in tacrolimus pharmacokinetics. In particular, polymorphisms in the gene encoding cytochrome P450 3A5 influence tacrolimus metabolism and may affect early dose requirements during the post-transplant period. Additionally, temporal fluctuations in tacrolimus exposure within individual patients are increasingly recognized as clinically relevant. Measures that capture the proportion of time during which concentrations remain within the therapeutic range provide a useful indicator of exposure stability.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Tacrolimus therapy after hematopoietic stem cell transplantation is influenced by molecular pharmacology, blood cell-dependent distribution, genetic determinants of metabolism, and temporal variability in drug exposure. Integrating these factors may improve understanding of therapeutic drug monitoring and promote more individualized strategies to maintain stable immunosuppression and improve transplant outcomes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s40780-026-00581-3","type":"journal-article","created":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T08:52:42Z","timestamp":1777711962000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Personalized tacrolimus therapy in allogeneic hematopoietic stem cell transplantation: from pharmacokinetic variability to novel control strategies"],"prefix":"10.1186","volume":"12","author":[{"given":"Naoki","family":"Yoshikawa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,2]]},"reference":[{"key":"581_CR1","doi-asserted-by":"publisher","first-page":"605726","DOI":"10.3389\/FIMMU.2021.605726","volume":"12","author":"M Gooptu","year":"2021","unstructured":"Gooptu M, Antin JH. 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