Addiction annually costs America >$500B. Narcotic addiction is especially worrisome since intravenous drug abuse (IVDA) also promotes HIV transmission. Reducing IVDA is critical to lowering the incidence of HIV. Since >75% of IVDA is with opioids, effective treatment of opiate addiction should markedly reduce IVDA and lower HIV transmission rates. Naltrexone has markedly lowered relapse rates and shortened treatment time in opiate-addicted patients when combined with standard behavioral therapies. This efficacy, however, is dependent upon strict adherence, and monitoring this adherence relies primarily upon directly observed therapy (DOT). The focus of this program is to develop a novel medication adherence monitoring system that can realistically monitor whether narcotic addicts actually ingest their oral naltrexone on a regular basis, completely independent of DOT. In this patented system, innocuous """"""""taggants"""""""" (chosen from FDA """"""""Generally Recognized as Safe"""""""" list) are """"""""packaged"""""""" with the active pharmaceutical ingredient (e.g., naltrexone) into a """"""""smart"""""""" drug formulation. After the drug is ingested and enters the stomach, the taggant is released and rapidly metabolized to a volatile metabolite. Detection of the volatile metabolite in the breath verifies oral ingestion of the drug. We previously established that this system, directed at accurately assessing adherence in humans, is technically feasible. Notable development findings include: 1) secondary (2o) alcohols (e.g., 2-butanol) are superior taggants metabolized by alcohol dehydrogenase (ADH is not subject to genetic polymorphisms, unlike the isoform) to generate volatile ketones (e.g., 2-butanone) exhaled in breath, 2) a miniature gas chromatography-metal oxide sensor (mGC-MOS) has been created to measure ketones in human breath, 3) multiple taggants can be readily incorporated into the system to monitor adherence for several drugs, and 4) food does not interfere with the system. We now propose to specifically adapt and expand this core technology to manage opioid-addicted patients with HIV/AIDS. To that end, the following 2 aims will be achieved:
Aim 1 : Create 8 SMART capsule-based naltrexone systems using 4 general types of pharma formulation strategies. Model naltrexone (50 mg) formulations containing the GRAS taggant, 2-butanol (25 or 40 mg) will be prepared and preliminary stability studies executed: Type 1) hydrophobic system, Type 2) hydrophilic system, Type 3) reverse micelle system, and Type 4) water-in-oil microemulsion system (Months 1-6).
Aim 2 : Select the best naltrexone formulation and test mGC-MOS performance in healthy volunteers in the UF Clinical and Translational Science Institute (CTSI). Using a double blind, randomized, crossover study design, the relationship between the breath concentration (measured via mGC-MOS and gas chromatography mass spectroscopy [GC-MS]) of 2-butanol (taggant) and 2-butanone (metabolite) versus time will be determined after the oral administration of 3 promising naltrexone formulations selected from Aim 1 or a positive control (Months 7-12).

Public Health Relevance

The goal of this Phase I SBIR program is to develop a novel breath-based medication adherence monitoring system that can realistically monitor whether opiate addicts with HIV/AIDS actually ingest (definitive adherence) their oral naltrexone on a regular basis, completely independent of the need for directly observed therapy.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Small Business Innovation Research Grants (SBIR) - Phase I (R43)
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Special Emphasis Panel (ZRG1-AARR-G (10))
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Park, Moo Kwang
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Xhale, Inc.
United States
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