# GOLDILOKs Project 1:  Clinical

> **NIH NIH P50** · CHILDREN'S MERCY HOSP (KANSAS CITY, MO) · 2020 · $349,365

## Abstract

Knowledge is limited regarding how ontogeny and genetic variation influence the expression of drug
targets and thereby contribute to variability in drug response in children. One challenge in
designing studies to acquire this knowledge is the extensive variability in drug exposure that occurs
in vivo, especially when drug clearance is dependent on a polymorphically expressed pathway. For
example, recently published data by our group demonstrated a 30-fold difference in systemic
exposure between CYP2D6 poor and ultrarapid metabolizers administered the same weight-based
dose (0.5 mg/kg) of atomoxetine (ATX), a medication used to treat ADHD. Therefore, we propose
that by eliminating inter-individual differences in dose-exposure we can identify patient-specific
characteristics that are predictive of response thereby creating a foundation for personalized drug
dosing guidelines. The aims of this project are to 1) identify the inherent characteristics of children
that segregate with ATX clinical response phenotypes, and 2) translate our understanding of the
individual characteristics that drive the ATX dose-exposure relationship to target therapeutic
exposures prior to a child's first dose. These aims will be accomplished by an investigation that
employs an individual genome-ontogeny informed pharmacokinetic (iGO-PK) model to control ATX
exposure between patients with state-of-the-art measures of outcome including pharmaco
metabolomic signatures, biomarkers of neurotransmitter activity, such as plasma
dihydroxyphenylglycol (DHPG) and change in pupil diameter as an indicator of central
norepinephrine transport (NET) inhibition by ATX, as well as comprehensive clinical assessment.
The proposed study will establish a new investigational paradigm that can be generally applied to
medications used for a diverse array of pediatric indications, and that allows physicians to choose
the safest and most effective dose of any drug that they prescribe for children.

## Key facts

- **NIH application ID:** 9976572
- **Project number:** 5P50HD090258-05
- **Recipient organization:** CHILDREN'S MERCY HOSP (KANSAS CITY, MO)
- **Principal Investigator:** Sarah Soden
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $349,365
- **Award type:** 5
- **Project period:** — → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9976572

## Citation

> US National Institutes of Health, RePORTER application 9976572, GOLDILOKs Project 1:  Clinical (5P50HD090258-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9976572. Licensed CC0.

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