# A physiologically based pharmacokinetic model of human airway epithelia

> **NIH FDA U01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2022 · $300,000

## Abstract

Abstract
 Inhaled drugs represent an important, effective, but often expensive therapeutic option for lung diseases
such as asthma or chronic obstructive pulmonary disease (COPD). Development of generic equivalents to brand
name inhaled drugs could reduce the financial burden associated with these agents but is limited by difficulties
performing pharmacokinetic (PK) bioequivalence studies on airway epithelia, the primary target of inhaled
agents. Although physiologically based pharmacokinetic (PBPK) models can serve as an alternative to direct
measurement of drug PK within airway epithelia, current models fail to account for the actions of drug
transporters and metabolizing enzymes that may influence the effective concentrations of inhaled drugs. To
address this gap, we have assembled a group of experts on airway epithelial cell culture, quantitative proteomics,
PBPK modeling, and PK testing of aerosolized drugs to systematically measure the protein levels of relevant
drug transporters and metabolizing enzymes within human airway epithelia. Our proposal takes advantage of
the robust Tissue Procurement and Cell Culture Core present at our institution that can provide us with primary
human airway epithelial cells for culture representing a wide range of demographic factors and anatomic
locations as well as in vivo tissue samples for testing. Our plan is to develop a comprehensive assessment of
the drug transporters and metabolizing enzymes present in airway epithelia based on literature review and
analysis of our own existing RNA sequencing databases, then utilize this data to develop quantitative targeted
absolute proteomic (QTAP) methods for measurement of the relevant proteins. This QTAP methodology will then
be applied to human airway epithelia representing a wide range of demographic features, anatomic locations,
and inflammatory states as well as tissues obtained in vivo. Ultimately, we will utilize this data to develop
enhanced PBPK models, which we will then test be tested via mass spectrometric analysis of test drug and drug
metabolites in apical, intracellular, and basolateral compartments after aerosolization onto airway epithelia.
Overall, the studies in this proposal will generate a comprehensive evaluation of the levels of drug transporters
and metabolizing enzymes in human airway epithelia and enhanced PBPK modeling that can support more rapid
development of generic versions of inhaled drugs.

## Key facts

- **NIH application ID:** 10459416
- **Project number:** 5U01FD007338-02
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Charles Richard Esther
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** FDA
- **Fiscal year:** 2022
- **Award amount:** $300,000
- **Award type:** 5
- **Project period:** 2021-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10459416

## Citation

> US National Institutes of Health, RePORTER application 10459416, A physiologically based pharmacokinetic model of human airway epithelia (5U01FD007338-02). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10459416. Licensed CC0.

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