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Interaction of disulfiram with antiretroviral medications: Efavirenz increases while atazanavir decreases disulfiram effect on enzymes of alcohol metabolism

Authors

  • Elinore F. McCance-Katz MD, PhD,

    Corresponding author
    1. University of California San Francisco, San Francisco, California
    • Address correspondence to Dr. McCance-Katz, Chief Medical Officer, Substance Abuse and Mental Health Services Administration, 1 Choke Cherry Rd., Room 8-1055, Rockville, MD 20857. E-mail: Elinore.McCance-Katz@samhsa.hhs.gov.

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  • Valerie A. Gruber PhD,

    1. University of California San Francisco, San Francisco, California
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  • George Beatty MD, MPH,

    1. University of California San Francisco, San Francisco, California
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  • Paula Lum MD,

    1. University of California San Francisco, San Francisco, California
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  • Qing Ma PhD,

    1. HIV Clinical Pharmacology Research Program, Translational Pharmacology Research Core, NYS Center of Excellence in Bioinformatics and Life Sciences, University at Buffalo, SUNY, Buffalo, New York
    2. School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, SUNY, Buffalo, New York
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  • Robin DiFrancesco,

    1. HIV Clinical Pharmacology Research Program, Translational Pharmacology Research Core, NYS Center of Excellence in Bioinformatics and Life Sciences, University at Buffalo, SUNY, Buffalo, New York
    2. School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, SUNY, Buffalo, New York
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  • Jill Hochreiter,

    1. HIV Clinical Pharmacology Research Program, Translational Pharmacology Research Core, NYS Center of Excellence in Bioinformatics and Life Sciences, University at Buffalo, SUNY, Buffalo, New York
    2. School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, SUNY, Buffalo, New York
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  • Paul K. Wallace PhD,

    1. Department of Flow and Image Cytometry, Roswell Park Cancer Institute, Buffalo, New York
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  • Morris D. Faiman PhD,

    1. Department of Pharmacology and Toxicology, University of Kansas, Lawrence, Kansas
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  • Gene D. Morse PhD

    1. HIV Clinical Pharmacology Research Program, Translational Pharmacology Research Core, NYS Center of Excellence in Bioinformatics and Life Sciences, University at Buffalo, SUNY, Buffalo, New York
    2. School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, SUNY, Buffalo, New York
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Abstract

Background and Objectives

Alcohol abuse complicates treatment of HIV disease and is linked to poor outcomes. Alcohol pharmacotherapies, including disulfiram (DIS), are infrequently utilized in co-occurring HIV and alcohol use disorders possibly related to concerns about drug interactions between antiretroviral (ARV) medications and DIS.

Method

This pharmacokinetics study (n = 40) examined the effect of DIS on efavirenz (EFV), ritonavir (RTV), or atazanavir (ATV) and the effect of these ARV medications on DIS metabolism and aldehyde dehydrogenase (ALDH) activity which mediates the DIS-alcohol reaction.

Results

EFV administration was associated with decreased S-Methyl-N-N-diethylthiocarbamate (DIS carbamate), a metabolite of DIS (p = .001) and a precursor to the metabolite responsible for ALDH inhibition, S-methyl-N,N-diethylthiolcarbamate sulfoxide (DETC–MeSO). EFV was associated with increased DIS inhibition of ALDH activity relative to DIS alone administration possibly as a result of EFV-associated induction of CYP 3A4 which metabolizes the carbamate to DETC–MeSO (which inhibits ALDH). Conversely, ATV co-administration reduced the effect of DIS on ALDH activity possibly as a result of ATV inhibition of CYP 3A4. DIS administration had no significant effect on any ARV studied.

Discussion/Conclusions

ATV may render DIS ineffective in treatment of alcoholism.

Future Directions

DIS is infrequently utilized in HIV-infected individuals due to concerns about adverse interactions and side effects. Findings from this study indicate that, with ongoing clinical monitoring, DIS should be reconsidered given its potential efficacy for alcohol and potentially, cocaine use disorders, that may occur in this population. (Am J Addict 2014;23:137–144)

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