Date: Monday, May 4, 2015
Session Time: 5:30pm-6:30pm
Presentation Time: 5:30pm-6:30pm
Location: Exhibit Hall E
Immunosuppressive drugs such as tacrolimus have narrow therapeutic ranges and their dosing variability necessitates intensive drug monitoring. This study aimed to use Feedback System Control (FSC), a mechanism-independent personalized medicine platform that rationally reconciles phenotypic responses to therapeutic intervention, to prescribe patient-specific drug regimens with rapid convergence towards target serum levels (1, 2).
MATERIALS & METHODS:
We retrospectively collected tacrolimus dose and serum trough levels for 6 patients. Initially, target serum drug levels were established and FSC optimization was performed whereby patient-specific therapeutic response constants, or indicators of how that specific patient's serum drug levels would respond to drug dosing, were determined. These constants were then utilized for subsequent dosing optimization.
Patient tacrolimus dosages ranged from 0.5-2 mg, resulting in serum levels of 4.8-16.2 ng/ml. FSC stably converged into and stayed within the target tacrolimus range of 8-10 ng/ml at day 10, an improved response compared to a conventional regimen. Clinically-titrated and FSC-directed tacrolimus regimens were also compared. Of note, the FSC-optimized tacrolimus doses were different from those utilized clinically and were simultaneously capable of maintaining steady target serum levels over the entire course of treatment.
FSC formulated patient-specific optimal tacrolimus dosing regimens with rapid convergence into a specified target serum tacrolimus range based only on previous doses and blood levels. Given the phenotypically-driven nature of FSC, this powerful platform can robustly achieve therapeutic levels of an immunosuppressive drug with unprecedented personalization.
1. P.K. Wong, C.M. Ho, et al., PNAS, 2008
2. H. Tsutsui et al., Nat Comm, 2011.
To cite this abstract in AMA style:Zarrinpar A, Silva A, Lee D-K, Datta N, Ho C-M, Ho D. Phenotypic Personalized Medicine: Mechanism-Independent Convergence Into Target Serum Tacrolimus Levels for Optimized Liver Transplant Immunosuppression [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/phenotypic-personalized-medicine-mechanism-independent-convergence-into-target-serum-tacrolimus-levels-for-optimized-liver-transplant-immunosuppression/. Accessed September 30, 2020.
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