The Journal of Practical Medicine >

2026 , Vol. 42 >Issue 7: 1294 - 1300

DOI: https://doi.org/10.3969/j.issn.1006-5725.2026.07.024

Reviews

Research advances in personalized tacrolimus therapy for adult liver transplant recipients

  • Yan JIANG ,
  • Guohui WANG ,
  • Cangsang SONG ,
  • Hanshu ZHANG ,
  • Xingde LI
Expand
  • 1.Department of Pharmacy，Ganmei Hospital Affiliated to Kunming Medical University，Kunming 650224，Yunnan，China
    2.Graduate School of Kunming Medical University，Kunming 650500，Yunnan，China

Received date: 2025-07-21

  Revised date: 2025-09-16

  Accepted date: 2025-09-17

  Online published: 2026-04-13

Fold

Abstract

Tacrolimus（TAC） serves as a cornerstone immunosuppressive therapy following liver transplantation（LT）. However， its narrow therapeutic window， combined with significant inter- and intra-individual pharmacokinetic variability， often leads to blood concentrations deviating from target range， posing a major challenge for precision dosing. In recent years， with the widespread adoption of therapeutic drug monitoring（TDM）， research on individualized dosing strategies based on TAC blood concentrations has achieved substantial progress. This article provides a systematic review of the latest advances in personalized TAC dosing for adult LT recipients， with a focus on the clinical application value and current status of pharmacogenomics， population pharmacokinetics（PPK）， and machine learning（ML）. It further compares and summarizes the strengths and limitations of different modeling strategies. Studies demonstrate that model-informed precision dosing（MIPD） tools can not only significantly enhance the accuracy of blood concentration predictions but also generate patient-tailored dosing regimens， thereby contributing to the optimization of therapeutic outcomes and long-term prognosis in LT patients.

Key words： tacrolimus; liver transplantation; personalized dosing; population pharmacokinetics; machine learning

Cite this article

Yan JIANG , Guohui WANG , Cangsang SONG , Hanshu ZHANG , Xingde LI . Research advances in personalized tacrolimus therapy for adult liver transplant recipients[J]. The Journal of Practical Medicine, 2026 , 42(7) : 1294 -1300 . DOI: 10.3969/j.issn.1006-5725.2026.07.024

References

[1] BONNEY G K， CHEW C A， LODGE P， et al. Liver transplantation for non-resectable colorectal liver metastases： The International Hepato-Pancreato-Biliary Association consensus guidelines［J］. Lancet Gastroenterol Hepatol， 2021， 6（11）： 933-946. doi： 10.1016/S2468-1253（21）00219-3 .
[2] 蒋勇， 冯啸， 刘炜， 等. 2024年全球肝移植研究年度盘点——技术突破、精准管理与未来挑战［J］. 器官移植， 2025， 16（3）： 350-358. doi： 10.12464/j.issn.1674-7445.2025099 .
[3] HUANG H， LU Y， ZHOU T， et al. Innate Immune Cells in Immune Tolerance After Liver Transplantation［J］. Front Immunol， 2018， 9： 2401. doi： 10.3389/fimmu.2018.02401 .
[4] OHM B， GIANNOU A D， HARRIMAN D， et al. Chimerism and immunological tolerance in solid organ transplantation［J］. Semin Immunopathol， 2025， 47（1）： 27. doi： 10.1007/s00281-025-01052-x .
[5] LAN T， WU G， ZUO B， et al. Regulation of the immune microenvironment and immunotherapy after liver transplantation［J］. Front Immunol， 2025， 16： 1602877. doi： 10.3389/fimmu.2025.1602877 .
[6] LEVITSKY J， GOLDBERG D， SMITH A R， et al. Acute Rejection Increases Risk of Graft Failure and Death in Recent Liver Transplant Recipients［J］. Clin Gastroenterol Hepatol， 2017， 15（4）： 584-593.e582. doi： 10.1016/j.cgh.2016.07.035 .
[7] HARRINGTON CR， BITTERMANN T， GOLDBERG D， et al. The Continued Impact of Acute Rejection in the Last Decade of Liver Transplantation［J］. Gastro Hep Adv， 2022， 1（5）： 686-688. doi： 10.1016/j.gastha.2022.04.021 .
[8] ONG S C， GASTON R S. Thirty Years of Tacrolimus in Clinical Practice［J］. Transplantation， 2021， 105（3）： 484-495. doi： 10.1097/TP.0000000000003350 .
[9] 陈冰， 左笑丛， 李新刚， 等. 模型引导的抗排异治疗患者他克莫司精准用药专家共识［J］. 中国临床药理学与治疗学， 2025， 30（04）： 433-445. doi： 10.12092/j.issn.1009-2501.2025.04.001 .
[10] CAMPAGNE O， MAGER D E， TORNATORE K M. Population Pharmacokinetics of Tacrolimus in Transplant Recipients： What Did We Learn About Sources of Interindividual Variabilities？［J］. J Clin Pharmacol， 2019， 59（3）： 309-325. doi： 10.1002/jcph.1325 .
[11] KHONG J， LEE M， WARREN C， et al. Tacrolimus dosing in liver transplant recipients using phenotypic personalized medicine： A phase 2 randomized clinical trial［J］. Nat Commun， 2025， 16（1）： 4558. doi： 10.1038/s41467-025-59739-6 .
[12] ZHOU X， TANG R， ZHANG D， et al. Effect of CYP 3A4*1B and CYP3A5*3 Gene Polymorphisms in Antirejection of Tacrolimus in Liver Transplant Patients［J］. Transplant Proc， 2025， 57（2）： 298-304. doi： 10.1016/j.transproceed.2024.10.030 .
[13] TANG H L， XIE H G， YAO Y， et al. Lower tacrolimus daily dose requirements and acute rejection rates in the CYP3A5 nonexpressers than expressers［J］. Pharmacogenet Genomics， 2011， 21（11）： 713-720. doi： 10.1097/FPC.0b013e32834a48ca .
[14] BUENDíA J A， HALAC E， BOSALEH A， et al. Frequency of CYP3A5 Genetic Polymorphisms and Tacrolimus Pharmacokinetics in Pediatric Liver Transplantation［J］. Pharmaceutics， 2020， 12（9）. doi： 10.3390/pharmaceutics12090898 .
[15] KIM J M， RYU J H， LEE K W， et al. Effect of CYP3A5 on the Once-Daily Tacrolimus Conversion in Stable Liver Transplant Patients［J］. J Clin Med， 2020， 9（9）. doi： 10.3390/jcm9092897 .
[16] SHAO J， WANG C， FU P， et al. Impact of Donor and Recipient CYP3A5*3 Genotype on Tacrolimus Population Pharmacokinetics in Chinese Adult Liver Transplant Recipients［J］. Ann Pharmacother， 2020， 54（7）： 652-661. doi： 10.1177/1060028019897050 .
[17] DONG Y， XU Q， LI R， et al. CYP3A7， CYP3A4， and CYP3A5 genetic polymorphisms in recipients rather than donors influence tacrolimus concentrations in the early stages after liver transplantation［J］. Gene， 2022， 809： 146007. doi： 10.1016/j.gene.2021.146007 .
[18] LINDARTE E F， DE JESUS VASQUEZ G， TORO RENDóN L G， et al. Effect of CYP3A5 genotypes on pharmacokinetic of tacrolimus in colombian liver transplant patients［J］. Front Pharmacol， 2025， 16： 1505490. doi： 10.3389/fphar.2025.1505490 .
[19] NALDI G A R， MINARI A B， PEREIRA T D M， et al. CYP3A5 and POR gene polymorphisms as predictors of infection and graft rejection in post-liver transplant patients treated with tacrolimus - a cohort study［J］. Pharmacogenomics J， 2025， 25（2）： 4. doi： 10.1038/s41397-025-00363-4 .
[20] SHI B， LIU Y， LIU D， et al. Genotype-guided model significantly improves accuracy of tacrolimus initial dosing after liver transplantation［J］. E Clinl Med， 2023， 55： 101752. doi： 10.1016/j.eclinm.2022.101752 .
[21] YOON S B， LEE J M， JUNG C W， et al. Machine-learning model to predict the tacrolimus concentration and suggest optimal dose in liver transplantation recipients： A multicenter retrospective cohort study［J］. Sci Rep， 2024， 14（1）： 19996. doi： 10.1038/s41598-024-71032-y .
[22] WOILLARD J B， LABRIFFE M， DEBORD J， et al. Tacrolimus Exposure Prediction Using Machine Learning［J］. Clin Pharmacol Ther， 2021， 110（2）： 361-369. doi： 10.1002/cpt.2123 .
[23] 沈黎， 李智平. 儿童他克莫司个体化给药模型的研究进展［J］. 中国药房， 2025， 36（01）： 124-128. doi 10.6039/j.issn.1001-0408.2025.01.21.
[24] SONG X， LIU F， GAO H， et al. Compare the performance of multiple machine learning models in predicting tacrolimus concentration for infant patients with living donor liver transplantation［J］. Pediatr Transplant， 2023， 27（1）： e14379. doi： 10.1111/petr.14379 .
[25] 刘迎春， 杨斌. 人工智能在肝移植中的应用研究进展［J］. 器官移植， 2024， 15（06）： 883-888. doi： 10.3969/j.issn.1674-7445.2024084 .
[26] LU Z， BONATE P， KEIRNS J. Population pharmacokinetics of immediate- and prolonged-release tacrolimus formulations in liver， kidney and heart transplant recipients［J］. Br J Clin Pharmacol， 2019， 85（8）： 1692-1703. doi： 10.1111/bcp.13952 .
[27] CHEN B， SHI H Q， LIU X X， et al. Population pharmacokinetics and Bayesian estimation of tacrolimus exposure in Chinese liver transplant patients［J］. J Clin Pharm Ther， 2017， 42（6）： 679-688. doi： 10.1111/jcpt.12599 .
[28] JALIL M H， HAWWA A F， MCKIERNAN P J， et al. Population pharmacokinetic and pharmacogenetic analysis of tacrolimus in paediatric liver transplant patients［J］. Br J Clin Pharmacol， 2014， 77（1）： 130-140. doi： 10.1111/bcp.12174 .
[29] LEE D R， HO M J， JUNG H J， et al. Enhanced dissolution and oral absorption of tacrolimus by supersaturable self-emulsifying drug delivery system［J］. Int J Nanomedicine， 2016， 11： 1109-1117. doi： 10.2147/IJN.S102991 .
[30] ZHANG Y， SHANGGUAN C， ZHANG X， et al. Computer-Aided Diagnosis of Complications After Liver Transplantation Based on Transfer Learning［J］. Interdiscip Sci， 2024， 16（1）： 123-140. doi： 10.1007/s12539-023-00588-6 .
[31] ZHANG H X， SHENG C C， LIU L S， et al. Systematic external evaluation of published population pharmacokinetic models of mycophenolate mofetil in adult kidney transplant recipients co-administered with tacrolimus［J］. Br J Clin Pharmacol， 2019， 85（4）： 746-761. doi： 10.1111/bcp.13850 .
[32] CAI X， LI R， SHENG C， et al. Systematic external evaluation of published population pharmacokinetic models for tacrolimus in adult liver transplant recipients［J］. Eur J Pharm Sci， 2020， 145： 105237. doi： 10.1016/j.ejps.2020.105237 .
[33] LI Z R， LI R D， NIU W J， et al. Population Pharmacokinetic Modeling Combined With Machine Learning Approach Improved Tacrolimus Trough Concentration Prediction in Chinese Adult Liver Transplant Recipients［J］. J Clin Pharmacol， 2023， 63（3）： 314-325. doi： 10.1002/jcph.2156 .
[34] HOFFERT Y， DIA N， VANUYTSEL T， et al. Correction： Model-Informed Precision Dosing of Tacrolimus： A Systematic Review of Population Pharmacokinetic Models and a Benchmark Study of Software Tools［J］. Clin Pharmacokinet， 2024， 63（10）： 1511. doi： 10.1007/s40262-024-01438-4 .
[35] ZHU L， YANG J， ZHANG Y， et al. Effects of CYP3A5 genotypes， ABCB1 C3435T and G2677T/A polymorphism on pharmacokinetics of Tacrolimus in Chinese adult liver transplant patients ［J］. Xenobiotica， 2015， 45（9）： 840-846. doi： 10.3109/00498254.2015.1021733 .
[36] JI E， KIM M G， OH J M. CYP3A5 genotype-based model to predict tacrolimus dosage in the early postoperative period after living donor liver transplantation［J］. Ther Clin Risk Manag， 2018， 14： 2119-2126. doi： 10.2147/TCRM.S184376 .
[37] DU Y， SONG W， XIONG X， et al. Population pharmacokinetics and dosage optimisation of tacrolimus coadministration with Wuzhi capsule in adult liver transplant patients［J］. Xenobiotica， 2022， 52（3）： 274-283. doi： 10.1080/00498254.2022.2073851 .
[38] HOU J， YANG S， LIU W， et al. Tacrolimus population pharmacokinetic model-informed precision dosing in adult liver transplant patients［J］. Naunyn Schmiedebergs Arch Pharmacol， 2025， 398（8）： 10719-10729. doi： 10.1007/s00210-025-03982-7 .
[39] KOMENKUL V， SUKARNJANASET W， KOMOLMIT P， et al. External validation of population pharmacokinetic models of tacrolimus in Thai adult liver transplant recipients［J］. Eur J Clin Pharmacol， 2024， 80（8）： 1229-1240. doi： 10.1007/s00228-024-03692-8 .
[40] ZHU H， WANG M， XIONG X， et al. Plasma metabolomic profiling reveals factors associated with dose-adjusted trough concentration of tacrolimus in liver transplant recipients［J］. Front Pharmacol， 2022， 13： 1045843. doi： 10.3389/fphar.2022.1045843 .
Options
Outlines

/

〈 〉