Medical College of Wisconsin
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Tacrolimus dosing in liver transplant recipients using phenotypic personalized medicine: A phase 2 randomized clinical trial. Nat Commun 2025 May 16;16(1):4558

Date

05/17/2025

Pubmed ID

40379675

Pubmed Central ID

PMC12084539

DOI

10.1038/s41467-025-59739-6

Scopus ID

2-s2.0-105005401352 (requires institutional sign-in at Scopus site)   2 Citations

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.

Author List

Khong J, Lee M, Warren C, Kim UB, Duarte S, Andreoni KA, Shrestha S, Johnson MW, Battula NR, McKimmy DM, Beduschi T, Lee JH, Li DM, Ho CM, Zarrinpar A

Author

Narendra Battula MD Associate Professor in the Surgery department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Adult
Aged
Female
Graft Rejection
Humans
Immunosuppressive Agents
Liver Transplantation
Male
Middle Aged
Phenotype
Precision Medicine
Tacrolimus
Transplant Recipients