Tacrolimus dosing in liver transplant recipients using phenotypic personalized medicine: A phase 2 randomized clinical trial
- Jeffrey Khong
- Megan Lee
- Curtis Warren
- Un Bi Kim
- Sergio Duarte
- Kenneth A. Andreoni
- Sunaina Shrestha
- Mark W. Johnson
- Narendra R. Battula
- Danielle M. McKimmy
- Thiago Beduschi
- Ji-Hyun Lee
- Derek M. Li
- Chih-Ming Ho
- Ali Zarrinpar
2025-05-16
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.