# Interindividual Variability in Drug Metabolism in Ethnically Diverse Populations

> **NIH NIH R35** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2024 · $381,394

## Abstract

PROJECT SUMMARY
Differences in drug metabolism between patients can significantly affect drug concentrations in the body and
overall drug response (efficacy and toxicity). Advances in pharmacogenomics have improved our understanding
of how variations in genes that encode drug metabolizing enzymes (e.g., cytochrome P450 enzymes) affect drug
response, primarily in European ancestry populations. However, far less is known about the mechanisms and
clinical consequences of genetic and non-genetic factors (sex, age, ethnicity, epigenetics, drug interactions, etc.)
that affect drug disposition in patients from understudied ethnic backgrounds. Inadequate representation of
diverse ancestral populations in both basic and translational pharmacogenomics and multi-omics studies is a
key barrier to the implementation of precision medicine for all patients. Recent findings from my laboratory
support the contention that genetic and phenotypic markers are needed to accurately assess individual drug
metabolism capacity. The overall vision of my research program is to understand the underlying mechanisms
of interindividual variability in drug metabolism and drug response to advance precision medicine in ethnically
diverse patient populations. Through this Maximizing Investigators’ Research Award (MIRA R35) for Early Stage
Investigators, my research program will address key questions and important challenges in the field through the
following distinct and complementary projects. Project 1 will test the hypothesis that the inclusion of diverse
genetic ancestry populations in pharmacogenetics studies will provide greater insight into the underlying
mechanisms of interindividual variability in drug metabolism and response. Project 2 will test the hypothesis
that the application of an integrated pharmaco-omics approach will greatly enhance the ability to precisely
quantify drug metabolism capacity in individuals from diverse ethnic backgrounds. Project 3 will test the
hypothesis that the incorporation of data from mechanistic drug metabolism studies from understudied ethnic
populations will improve the prediction of pharmacokinetic variability using data-informed physiologically based
pharmacokinetic models compared to model predictions using European-based “reference” populations.
Significance: This research promises to shift the current “one-size-fits-all” drug dosing paradigm by utilizing and
integrating population-specific genetic variants and phenotypic biomarkers to accurately quantify individual drug
metabolism capacity, a major predictor of drug response, in understudied ethnic populations. My research
program will increase the return on investment for precision medicine initiatives by overcoming the barriers that
have limited the applicability of European-based genotype-guided dosing. This work will lay the foundation
needed to implement the right drug at the right dose for the right patient at the right time. This research represents
the first comprehensive ph...

## Key facts

- **NIH application ID:** 10873264
- **Project number:** 5R35GM143044-04
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Klarissa D. Jackson
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $381,394
- **Award type:** 5
- **Project period:** 2021-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10873264

## Citation

> US National Institutes of Health, RePORTER application 10873264, Interindividual Variability in Drug Metabolism in Ethnically Diverse Populations (5R35GM143044-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10873264. Licensed CC0.

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