# Formulation and pharmacokinetics of subcutaneous administration of deferiprone for prevention of chronic heart failure following hemorrhagic myocardial infarction.

> **NIH NIH R43** · CARDIO-THERANOSTICS LLC · 2023 · $390,028

## Abstract

Problem: Approximately 50% of myocardial infarction (MI) patients progress to chronic heart failure (CHF)
post-MI with a 5-year mortality rate of ~50% (>300,000 US deaths annually). Recent studies have elucidated
an obligate mechanism for progression to CHF and new therapeutic opportunities. The data indicate: 1) that
hemorrhage is associated with larger MIs; 2) when normalized for infarct size, patients with hemorrhagic MIs
(hMIs) are at greater risk for CHF; and 3) intramyocardial iron from hemorrhage persists for years and drives
persistent macrophage recruitment, inflammation, fat deposition, and loss of heart function. Extensive data
demonstrate that deferiprone (a generic iron chelator FDA approved for iron overload in thalassemia patients)
renders iron functionally inert, suppresses fat deposition, reduces iron within hMI territories, and supports
anatomical and functional recovery away from CHF in a large animal model of hMI. Yet, deferiprone has an
exceptionally short half-life (1-2 hours). Even given 2- to 3-times daily, large gaps in blood levels (exposure) of
deferiprone are evident, with implications for gaps in suppression of disease progression and iron removal.
Also, deferiprone has low bioavailability due to ~70% first-pass metabolism in the liver to the inactive 3-O-
glucuronide metabolite, which may be associated with at least some (possibly most?) side effects. Solution:
We propose that subcutaneous delivery of deferiprone using an infusion pump will provide continuous blood
exposure to maintain iron in its inert state, will enable continuous iron removal, and will bypass first pass
metabolism and minimize exposure to deferiprone’s primary metabolite. We further propose that a lower dose
of deferiprone will prove highly efficacious. In Phase I SBIR studies, we will attain proof of concept that
subcutaneous (SC) administration of deferiprone is efficient for delivery of deferiprone while avoiding first-pass
metabolism. In Phase II SBIR studies, we will evaluate administration using as infusion pump, we will
determine the minimum dose for maximal efficacy, and we will attain initial safety data. Aim 1: We will
prepare deferiprone from available API sources for subcutaneous delivery using established methods for
optimal patient comfort and compliance. Purity of the API, oral, IV, and SC drug will be verified using
published HPLC methods and we will perform preliminary 1-month drug stability at ambient and accelerated
storage conditions. Aim 2: We will establish LC/MS methods to quantitate and identify deferiprone and its
metabolites and perform pharmacokinetic analysis of SC administration as compared to IV and oral delivery.
We anticipate >90% bioavailability of SC deferiprone (compared to IV), no first-pass metabolism, and dose-
linearity following SC administration. Impact: Foremost, this study holds the promise to be the first drug
capable of removing an obligate driver of CHF in post hMI patients. The product further holds t...

## Key facts

- **NIH application ID:** 10700370
- **Project number:** 1R43HL169094-01
- **Recipient organization:** CARDIO-THERANOSTICS LLC
- **Principal Investigator:** Robert E Finney
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $390,028
- **Award type:** 1
- **Project period:** 2023-06-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10700370

## Citation

> US National Institutes of Health, RePORTER application 10700370, Formulation and pharmacokinetics of subcutaneous administration of deferiprone for prevention of chronic heart failure following hemorrhagic myocardial infarction. (1R43HL169094-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10700370. Licensed CC0.

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