# Precision Pharmacokinetic-Guided Tacrolimus Dosing to Improve Pediatric Heart Transplant Outcomes

> **NIH NIH K01** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2020 · $167,448

## Abstract

ABSTRACT
Of the more than 400 children annually receiving a heart transplant, the likelihood that the child dies within five
years (25%) is equivalent to the potential that the child lives >20 years post-transplant. The success of the
transplant, and thus long-term survival of the child, is well known to correlate with achieving adequate
immunosuppression to prevent rejection, especially in the period immediately following transplant. Attaining
adequate immunosuppression is complicated by several factors, many of which impact the pharmacokinetics
(PK) of the immunosuppressive agent. These factors include age of the patient, renal and hepatic function,
concomitant medications, patient genetics, and the time post-transplant. Frequent, invasive drug monitoring is
used clinically to assess how these factors impact an individual child’s PK, and in turn the dose required to
achieve and maintain adequate immunosuppression. However, this empirical “guess and check” approach often
results in the child spending substantial time receiving immunosuppressive therapy that is either ineffective or
unsafe, decreasing the longevity of the transplant organ and thus, long-term patient survival. A more desirable
approach would be to guide dosing using a precision medicine approach, wherein patient specific factors are
used a priori to predict the dose most likely to achieve adequate immunosuppression. Developing a precision
medicine platform for immunosuppression following pediatric heart transplant has the potential to not only
improve outcomes in heart transplant recipients, but across all transplant types. This proposal aims to: 1)
determine the impact of CYP3A5 genetic variation on tacrolimus concentrations in children, 2) prospectively
validate the clinical utility of a PK-guided precision medicine platform in pediatric heart transplant patients
receiving tacrolimus-based immunosuppression; and 3) identify and correlate biomarkers of transplant outcomes
and tacrolimus safety/effect with the PK of tacrolimus, in order to establish the tacrolimus concentrations required
for safe and effective immunosuppression in pediatric heart transplant recipients. The overall objective of this
study is to improve the long-term survival of children with heart transplant via optimization of the child’s
immunosuppressive therapy. Importantly, the interdisciplinary nature of this mentored research proposal will
facilitate my progress towards an independent career developing precision medicine tools to improve health
outcomes in children.

## Key facts

- **NIH application ID:** 9977622
- **Project number:** 1K01HL148402-01A1
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Joseph Rower
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $167,448
- **Award type:** 1
- **Project period:** 2020-05-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9977622

## Citation

> US National Institutes of Health, RePORTER application 9977622, Precision Pharmacokinetic-Guided Tacrolimus Dosing to Improve Pediatric Heart Transplant Outcomes (1K01HL148402-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9977622. Licensed CC0.

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