# Application of Physiologically-Based Pharmacokinetic Modeling to Characterize Drug-Drug Interactions in Infants

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2022 · $491,626

## Abstract

ABSTRACT
Dedicated pharmacokinetic (PK) drug-drug interaction (DDI) studies are performed in healthy adult volunteers
during drug development. However, dedicated PK DDI studies are rarely performed in infants due to ethical and
logistical reasons. This results in the extrapolation of adult drug dosing recommendations that account for the
DDI potential to infants despite known age-induced physiological changes that can alter PK and affect the DDI
magnitude in infants. Physiologically-based pharmacokinetic (PBPK) models are an ideal tool to characterize PK
DDIs in infants because they can account for the DDI mechanism and physiological age-induced changes that
affect the DDI magnitude early in life. This proposal will evaluate a systematic approach to PK DDI evaluation in
infants using PBPK modeling and real-world data to accelerate the availability of age-appropriate drug dosing
recommendations in light of the DDI potential. We will characterize DDIs involving the cytochrome P450 (CYP)
3A substrates midazolam and fentanyl, and the CYP2C9/2C19 substrate phenobarbital, when co-administered
with drugs that inhibit their metabolism. We will validate the PBPK model DDI predictions using real-world data
collected from infants receiving the drug combinations per standard of care. The PBPK models will then guide
drug dosing that accounts for differences in DDI magnitude with age. Once our systematic approach to PBPK
model informed DDI evaluation in infants is established, it can be applied to characterize other PK DDIs and
accelerate the availability of drug dosing recommendations for infants in light of the DDI potential.

## Key facts

- **NIH application ID:** 10399613
- **Project number:** 5R01HD102949-02
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Daniel Gonzalez
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $491,626
- **Award type:** 5
- **Project period:** 2021-05-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10399613

## Citation

> US National Institutes of Health, RePORTER application 10399613, Application of Physiologically-Based Pharmacokinetic Modeling to Characterize Drug-Drug Interactions in Infants (5R01HD102949-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10399613. Licensed CC0.

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