# Precision Medicine in Pediatric Rehabilitation - Variability in Gabapentin Exposure

> **NIH NIH R03** · CHILDREN'S MERCY HOSP (KANSAS CITY, MO) · 2022 · $151,169

## Abstract

PROJECT SUMMARY
Although gabapentin is the most commonly prescribed medication for patients with neuropathic pain, the high
level of variability in reduction in pain limits effective treatment of pain. Work products from this grant would allow
the formation of a model-informed dosing strategy for this disorder. This research will have a lasting impact on
the way in which drugs are prescribed to pediatric patients with disabilities.
Medications which require transport across the blood-brain barrier (BBB) frequently require transport to reach
the cerebrospinal fluid (CSF). The gene SLC7A5 encodes for a light-chain protein (LAT1) that forms a
heterodimer with the a heavy chain protein CD98hc (encoded by SLC3A2) to create a membrane transport
protein referred to as the L-type amino acid transporter-1 (LAT1). 21 Previous in vitro studies have shown that
this transporter is one of the primary mechanisms of gabapentin transport across the BBB. This transporter is
also the confirmed or theorized transporter of several other commonly prescribed medications frequently
prescribed by rehabilitation providers.
Determining the variability in the amount of gabapentin a patient has in their plasma (systemic exposure) and
the amount that crosses the blood-brain-barrier (BBB) (central exposure) is significant to optimally determine the
most appropriate dose for each individual child (AIM1). The overall goal of my research strategy is to identify
factors influencing variability in central exposure (cerebrospinal fluid) in pediatric patients with CP. AIM 1
investigates the amount of central exposure by determining the amount of gabapentin that crosses the BBB. A
secondary portion of AIM 1 addresses the impact of the SCL7A5 gene (LAT1 transporter) by performing whole-
exome sequencing to evaluate the SLC7A5 gene and genotyping of selected single-nucleotide polymorphisms
in the intronic region of the LAT1 transporter.
AIM 2 is divided into two sub-aims using similar methodology. The first sub-aim evaluates the impact of
concurrently administered medications that also utilize the LAT1 transporter using a cell line model that is
transfected with the SLC7A5 gene to evaluate potential drug-drug interactions with commonly prescribed
medications in rehabilitation medicine, specifically levodopa, baclofen, and pregabalin. The second sub-aim of
AIM 2 involved transfection of genetic variants of the LAT1 transporter to determine the impact of coding region
changes to the function of this transporter. These variants may be informed by the whole-exome sequencing
variants found in AIM 1.
Both of these independent but complementary AIMs allows for data that will be incorporated within future decision
support tools to more appropriate anticipate what dose of gabapentin is needed to reach a desired level of
exposure and, subsequently, a desired level of clinical response (neuropathic pain reduction).

## Key facts

- **NIH application ID:** 10380258
- **Project number:** 1R03HD107642-01
- **Recipient organization:** CHILDREN'S MERCY HOSP (KANSAS CITY, MO)
- **Principal Investigator:** Matthew McLaughlin
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $151,169
- **Award type:** 1
- **Project period:** 2022-08-03 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10380258

## Citation

> US National Institutes of Health, RePORTER application 10380258, Precision Medicine in Pediatric Rehabilitation - Variability in Gabapentin Exposure (1R03HD107642-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10380258. Licensed CC0.

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