# Urine Colorimetry for Tuberculosis Pharmacokinetics Evaluation in Children and Adults

> **NIH NIH R01** · UNIVERSITY OF VIRGINIA · 2024 · $785,512

## Abstract

PROJECT SUMMARY/ABSTRACT
Tuberculosis (TB) is a major cause of morbidity and mortality worldwide with most deaths occurring in
individuals infected with highly treatable, drug sensitive stains. Individual pharmacokinetic variability is an
important driver of TB treatment failure particularly among undernourished populations, and sub-target serum
drug concentrations are associated with delayed response to treatment, death, and acquired bacterial drug
resistance. We have demonstrated that measuring an individual’s serum pharmacokinetics and personalizing a
dose adjustment can improve TB treatment outcomes. In TB endemic settings, medicines are typically only
available in fixed-dosed combination tablets as lack of cold chain preservation of serum and specialized
laboratory equipment hinder the timely measurement of drug concentrations. With the current 5R01 AI137080
we developed a process to quantify TB drug concentrations from urine analyzed with a benchtop
spectrophotometer bypassing the cold chain (Point-of-care Evaluation of Exposure to TB drugs- PEE-TB).
Focusing on rifampin for drug-susceptible TB, we found urinary rifampin excretion as measured by
spectrophotometry at feasible collection intervals predicted clinically significant targets of serum exposure of a
full dosing interval in children and adults with active TB. We also discovered that stool enteropathogen burden
at TB treatment initiation was associated with reduced rifampin serum exposures among children with
undernourishment and stool biomarkers suggested a malabsorption mechanism. Therefore, our central
hypothesis for this renewal is that in undernutrition related TB, pharmacokinetic variability is driven by the
burden of enteric pathogens via malabsorption, yet a clinically significant proportion of sub-target drug
concentrations can be corrected by measurement of urinary drug excretion. We propose a randomized and
controlled study of the PEE-TB based dose adjustment intervention for rifampin to test the efficacy of the
platform in increasing rifampin serum concentrations to target, and the overall safety of the dose
personalization strategy in children and adults. In this setting of high TB and undernutrition burden, the trial
design will also facilitate study of the mechanisms for pharmacokinetic variability including the presence of total
or species-specific enteropathogens, or enteropathy related to intestinal inflammation, functional intestinal
mass and intestinal permeability, and whether enteropathogens and/or enteropathy blunt the pharmacokinetic
response to PEE-TB based rifampin dose personalization.

## Key facts

- **NIH application ID:** 10802518
- **Project number:** 2R01AI137080-07
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Scott K Heysell
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $785,512
- **Award type:** 2
- **Project period:** 2018-09-24 → 2028-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10802518

## Citation

> US National Institutes of Health, RePORTER application 10802518, Urine Colorimetry for Tuberculosis Pharmacokinetics Evaluation in Children and Adults (2R01AI137080-07). Retrieved via AI Analytics 2026-06-14 from https://api.ai-analytics.org/grant/nih/10802518. Licensed CC0.

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