Document Type
Article
Publication Date
5-16-2025
Abstract
Tacrolimus is the most commonly used immunosuppression drug after solid organ transplantation; however, its dosing is challenging due to substantial inter-individual variability, often resulting in blood levels that deviate from the target therapeutic range. We explored whether a dynamically customized, phenotypic-outcome-guided drug dosing method could improve maintenance of drug trough levels within pre-determined target ranges, focusing on tacrolimus immediately after liver transplantation. This single-center, partially blinded, completed clinical trial involved 62 adults undergoing liver transplantation, block randomized into parallel groups: standard-of-care (SOC) clinician-determined or Phenotypic Personalized Medicine (PPM)-guided tacrolimus dosing. The primary outcome was percentage of post-transplant days with large (>2 ng/mL) deviations from the target range. At trial completion, analysis found statistically significant improvement in the PPM group (n = 27): 24.2% of days showing large deviations compared to 38.4% in the SOC group (n = 29) (difference -14.2%, 95% CI: -26.7 to -1.5 %, P = 0.029) with no increase in adverse events. These results demonstrate that PPM-guided tacrolimus dosing more effectively maintains drug levels within the target range compared to SOC, suggesting a promising approach to improving drug dosing. The trial was registered at ClinicalTrials.gov with the identifier NCT03527238.
Recommended Citation
Khong, Jeffrey; Lee, Megan; Warren, Curtis; Kim, Un; Duarte, Sergio; Andreoni, Kenneth; Shrestha, Sunaina; Johnson, Mark; Battula, Narendra; McKimmy, Danielle; Beduschi, Thiago; Lee, Ji-Hyun; Li, Derek; Ho, Chih-Ming; and Zarrinpar, Ali, "Tacrolimus Dosing in Liver Transplant Recipients Using Phenotypic Personalized Medicine: A Phase 2 Randomized Clinical Trial" (2025). Department of Surgery Faculty Papers. Paper 291.
https://jdc.jefferson.edu/surgeryfp/291
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This work is licensed under a Creative Commons Attribution 4.0 License.
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PubMed ID
40379675
Language
English
Included in
Chemical Actions and Uses Commons, Investigative Techniques Commons, Surgery Commons, Therapeutics Commons
Comments
This article is the author's final published version in Nature Communications, Volume 16, Issue 1, 2025, Article number 4558.
The published version is available at https://doi.org/10.1038/s41467-025-59739-6.
Copyright © The Author(s) 2025