On the disulfiram-like activity of moxalactam

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Abstract
A 3-way crossover study was undertaken in 10 healthy subjects to characterize the reported disulfiram-like activity of moxalactam and to assess its influence on ethanol and acetaldehyde metabolism. On different occasions separated by at least 2 wk, subjects were given in random order 0.5 g/kg ethanol orally, 0.5 g/kg ethanol following in 1 h by 1.0 g i.v. moxalactam and 1.0 g i.v. moxalactam every 8 h for 4 doses followed by 0.5 g/kg ethanol. Mean ethanol elimination rates of 13.1 .+-. 0.76, 10.1 .+-. 1.11 and 10.9 .+-. 1.06 mg/dl/h (mean .+-. SEM [standard error of the mean]) were observed in the 3 protocols, respectively. Corresponding mean estimated acetaldehyde clearance rates were 103.7 .+-. 15.55, 93.8 .+-. 13.79 and 97.3 .+-. 10.41 l/min (mean .+-. SEM). While no consistent moxalactam effect on ethanol or acetaldehyde elimination was observed, 2 subjects experienced mild disulfiram-like reactions to ethanol after moxalactam pretreament. In 1 subject, this reaction was associated with markedly elevated blood acetaldehyde concentrations. Thus, moxalactam pretreatment may induce a disulfiram-like reaction after ethanol ingestion, probably due to inhibition of aldehyde dehydrogenase; alcoholic beverages are contraindicated in patients receiving moxalactam. Apparently, such reactions will not occur when moxalactam is given after ethanol ingestion.

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