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

摘要: Background and Objectives Alcohol abuse complicates treatment of HIV disease is linked to poor outcomes. Alcohol pharmacotherapies, including disulfiram (DIS), are infrequently utilized in co-occurring alcohol use disorders possibly related concerns about drug interactions between antiretroviral (ARV) medications DIS. Method This pharmacokinetics study (n = 40) examined the effect DIS on efavirenz (EFV), ritonavir (RTV), or atazanavir (ATV) these ARV metabolism aldehyde dehydrogenase (ALDH) activity which mediates DIS-alcohol reaction. Results EFV administration was associated with decreased S-Methyl-N-N-diethylthiocarbamate (DIS carbamate), a metabolite (p = .001) precursor responsible for ALDH inhibition, S-methyl-N,N-diethylthiolcarbamate sulfoxide (DETC–MeSO). EFV increased inhibition relative alone as result EFV-associated induction CYP 3A4 metabolizes carbamate DETC–MeSO (which inhibits ALDH). Conversely, ATV co-administration reduced 3A4. had no significant any studied. Discussion/Conclusions ATV may render ineffective alcoholism. Future Directions DIS HIV-infected individuals due adverse side effects. Findings from this indicate that, ongoing clinical monitoring, should be reconsidered given its potential efficacy potentially, cocaine disorders, that occur population. (Am J Addict 2014;23:137–144)