Faculty Collaboration Database

Individualizing liver transplant immunosuppression using a phenotypic personalized medicine platform. Sci Transl Med 2016 Apr 06;8(333):333ra49

Date

04/08/2016

Pubmed ID

27053773

DOI

10.1126/scitranslmed.aac5954

Scopus ID

2-s2.0-84963491185 (requires institutional sign-in at Scopus site)   83 Citations

Abstract

Posttransplant immunosuppressive drugs such as tacrolimus have narrow therapeutic ranges. Inter- and intraindividual variability in dosing requirements conventionally use physician-guided titrated drug administration, which results in frequent deviations from the target trough ranges, particularly during the critical postoperative phase. There is a clear need for personalized management of posttransplant regimens to prevent adverse events and allow the patient to be discharged sooner. We have developed the parabolic personalized dosing (PPD) platform, which is a surface represented by a second-order algebraic equation with experimentally determined coefficients of the equation being unique to each patient. PPD uses clinical data, including blood concentrations of tacrolimus--the primary phenotypic readout for immunosuppression efficacy--to calibrate these coefficients and pinpoint the optimal doses that result in the desired patient-specific response. In this pilot randomized controlled trial, we compared four transplant patients prospectively treated with tacrolimus using PPD with four control patients treated according to the standard of care (physician guidance). Using phenotype to personalize tacrolimus dosing, PPD effectively managed patients by keeping tacrolimus blood trough levels within the target ranges. In a retrospective analysis of the control patients, PPD-optimized prednisone and tacrolimus dosing improved tacrolimus trough-level management and minimized the need to recalibrate dosing after regimen changes. PPD is independent of disease mechanism and is agnostic of indication and could therefore apply beyond transplant medicine to dosing for cancer, infectious diseases, and cardiovascular medicine, where patient response is variable and requires careful adjustments through optimized inputs.

Author List

Zarrinpar A, Lee DK, Silva A, Datta N, Kee T, Eriksen C, Weigle K, Agopian V, Kaldas F, Farmer D, Wang SE, Busuttil R, Ho CM, Ho D

Author

Calvin Martin Eriksen MD Assistant Professor in the Surgery department at Medical College of Wisconsin

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

Case-Control Studies
Computer Simulation
Dose-Response Relationship, Drug
Humans
Immunosuppressive Agents
Liver Transplantation
Phenotype
Physicians
Precision Medicine
Prednisone
Retrospective Studies
Tacrolimus
Treatment Outcome