title: Interaction of disulfiram with antiretroviral medications: efavirenz increases while atazanavir decreases disulfiram effect on enzymes of alcohol metabolism.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  ATV may render DIS ineffective in treatment of alcoholism.
  
  
  CONCLUSIONS
  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.
authors.affiliation: University of California San Francisco, San Francisco, California.
authors.forename: Elinore F
authors.initials: EF
authors.lastname: McCance-Katz
authors.forename: Valerie A
authors.initials: VA
authors.lastname: Gruber
authors.forename: George
authors.initials: G
authors.lastname: Beatty
authors.forename: Paula
authors.initials: P
authors.lastname: Lum
authors.forename: Qing
authors.initials: Q
authors.lastname: Ma
authors.forename: Robin
authors.initials: R
authors.lastname: DiFrancesco
authors.forename: Jill
authors.initials: J
authors.lastname: Hochreiter
authors.forename: Paul K
authors.initials: PK
authors.lastname: Wallace
authors.forename: Morris D
authors.initials: MD
authors.lastname: Faiman
authors.forename: Gene D
authors.initials: GD
authors.lastname: Morse
mesh_terms: D000328:Adult; D000427:Alcohol Deterrents / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D000437:Alcoholism / Q000188:drug therapy; D000444:Aldehyde Dehydrogenase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000480:Alkynes; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D000069446:Atazanavir Sulfate; D048588:Benzoxazines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D001711:Biotransformation / Q000187:drug effects; D003521:Cyclopropanes; D004221:Disulfiram / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology* / Q000627:therapeutic use; D004050:Ditiocarb / Q000031:analogs & derivatives / Q000378:metabolism; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D000431:Ethanol / Q000378:metabolism*; D005260:Female; D006207:Half-Life; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D011725:Pyridines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D019438:Ritonavir / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D013859:Thiocarbamates / Q000378:metabolism
chemical_list: D000427:Alcohol Deterrents; D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D009842:Oligopeptides; D011725:Pyridines; D013859:Thiocarbamates; C073220:S-methyl N,N-diethylthiolcarbamate sulfoxide; C070631:S-methyl diethylthiocarbamate; D000431:Ethanol; D000069446:Atazanavir Sulfate; D004050:Ditiocarb; D000444:Aldehyde Dehydrogenase; C098320:efavirenz; D019438:Ritonavir; D004221:Disulfiram