Lack of disulfiram-like reaction with metronidazole and ethanol.
BACKGROUND
Metronidazole, an effective antianaerobic agent, has been reported to have aversive properties when ingested with ethanol. This is thought to be due to the blocking of hepatic aldehyde dehydrogenase (ALDH) enzyme followed by the accumulation of acetaldehyde in the blood. However, based on animal studies and on only 10 human case reports, the existence of metronidazole-related disulfiram-like reaction has recently been questioned.


OBJECTIVE
To investigate the possible disulfiram-like properties of metronidazole and ethanol in human volunteers.


METHODS
Of 12 healthy male volunteers in this double-blind study, one-half received metronidazole for 5 days and the other half received placebo. All volunteers received ethanol 0.4 g/kg at the beginning of the study. Repeated blood samples were taken every 20 minutes for 4 hours, and blood acetaldehyde and ethanol concentrations were determined. Blood pressure, heart rate, and skin temperature were also measured every 20 minutes for objective signs of a possible disulfiram-like reaction. Volunteers also completed a questionnaire focusing on the subjective signs of disulfiram-like reaction.


RESULTS
Metronidazole did not raise blood acetaldehyde or have any objective or subjective adverse effects when used together with ethanol.


CONCLUSIONS
This study shows that metronidazole does not have an effect on blood acetaldehyde concentrations when ingested with ethanol and does not have any objective or subjective disulfiram-like properties. However, it is possible that disulfiram-like reaction can occur in some subgroups and by other mechanisms than the inhibition of hepatic ALDH.
Visapää
Jukka-Pekka
JP
Research Unit of Substance Abuse Medicine, Helsinki University Central Hospital, Finland.
Tillonen
Jyrki S
JS
Kaihovaara
Pertti S
PS
Salaspuro
Mikko P
MP
D000079:Acetaldehyde / Q000097:blood; D000328:Adult; D000427:Alcohol Deterrents / Q000009:adverse effects / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D004221:Disulfiram / Q000009:adverse effects*; D004311:Double-Blind Method; D004347:Drug Interactions; D000431:Ethanol / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008795:Metronidazole / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology*; D011795:Surveys and Questionnaires
D000427:Alcohol Deterrents; D008795:Metronidazole; D000431:Ethanol; D000079:Acetaldehyde; D004221:Disulfiram