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Lack of disulfiram-like reaction with metronidazole and ethanol
Jukka-Pekka Visapää1, Jyrki S Tillonen, Pertti S Kaihovaara
1Research Unit of Substance Abuse Medicine, Helsinki University Central Hospital, Finland.
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.
Insights
Metronidazole does not cause a disulfiram-like reaction when taken with alcohol. This study found no increase in acetaldehyde or adverse effects in human volunteers, questioning previous assumptions.
Area of Science:
- Pharmacology
- Toxicology
- Clinical Research
Background:
- Metronidazole, an antibiotic, is suspected to cause adverse reactions with ethanol due to acetaldehyde accumulation.
- Previous evidence is limited to animal studies and few human case reports, prompting re-evaluation.
Purpose of the Study:
- To investigate the disulfiram-like properties of metronidazole when co-ingested with ethanol in human volunteers.
Main Methods:
- A double-blind, placebo-controlled study involving 12 healthy males.
- Volunteers received either metronidazole or placebo, followed by ethanol (0.4 g/kg).
- Blood acetaldehyde and ethanol levels, vital signs, and subjective symptoms were monitored over 4 hours.
Main Results:
- Metronidazole did not elevate blood acetaldehyde levels when combined with ethanol.
- No objective (blood pressure, heart rate) or subjective adverse effects were observed.
Conclusions:
- Metronidazole does not appear to induce a disulfiram-like reaction via acetaldehyde accumulation in healthy individuals.
- The possibility of disulfiram-like reactions in specific subgroups or through alternative mechanisms warrants further investigation.
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