# Optimization of Bile Sequestrants to Treat Superwarfarin Poisoning

> **NIH NIH U01** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2022 · $673,844

## Abstract

Superwarfarins, also called long acting anticoagulant rodenticides (LAARs) are modified forms of the
anti-coagulant warfarin, developed as potent rodenticides in the 1970's when rodents developed
resistance to warfarin. LAARs are up to 100-fold more potent than warfarin and have extremely long
half-lives (20 days or longer); one of the most commonly used is Brodifacoum (BDF). Increased use of
LAARs led to an increase in accidental poisonings, mainly in young children. Those poisonings, which
contain low amounts of BDF, are typically treated by providing plasma that contains clotting factors,
and giving Vitamin K1 supplements for a few days. However, larger exposures occur due to
unintentional (e.g. accidental spills) and intentional (e.g. suicide and homicide attempts) reasons; and
LAARs have been used in terroristic and military attempts to cause injury and death on civilians and
military, most recently by contamination of synthetic cannabinoids causing up to 400 hospitalizations
and several deaths. While VK1 is used to prevent mortality from bleeding, it does not clear BDF from
the body, so treatment can require up to a year at extremely high cost, nor does it reduce VK1-
independent LAAR toxic actions which can lead to neuropathology and kidney damage. In previous
studies we showed that treatment of BDF poisoned rabbits with cholestyramine (CSA), an FDA
approved bile sequestrant which prevents enterohepatic recirculation, increased survival from 33% to
90%. This proposal expands upon those studies, with the overall goal to develop CSA as a
countermeasure for LAAR poisoning to rapidly eliminate LAARs from the body. Studies will be done to
optimize the amount and timing of CSA needed to increase elimination in adult rabbits, using different
amounts of BDF as well as other LAARs; and the amounts needed to prevent the induction of kidney
damage and neuropathology. Studies will be done to confirm CSA causes LAAR clearance in both
male and female rabbits, and is able to prevent any consequences to neonates due to prenatal
exposure of pregnant rabbits. Positive findings will provide the basis for eventual clinical testing of CSA
in poisoned patients.

## Key facts

- **NIH application ID:** 10488982
- **Project number:** 1U01NS127746-01
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** Douglas L. Feinstein
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $673,844
- **Award type:** 1
- **Project period:** 2022-09-20 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10488982

## Citation

> US National Institutes of Health, RePORTER application 10488982, Optimization of Bile Sequestrants to Treat Superwarfarin Poisoning (1U01NS127746-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10488982. Licensed CC0.

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