A study on the mechanism of disulfiram-like reactions induced by cephalosporins with different structures
Objective To investigate whether there is a difference in the mechanism of disulfiram-ethanol reaction(DLR)produced by the combination of cephalosporins with different structures,cefoperazone and ceftazidime,and ethanol.Methods A toxicity model for DLR induced by alcohol consumption was established after administration of cefoperazone or ceftazidime.The concentrations of ethanol and acetaldehyde in the blood were detected at various time points,and the toxic metabolic kinetic parameters were calculated using the DAS3.2.8 pharmacokinetic software.The activities of hepatic alcohol dehydrogenase(ADH)and aldehyde dehydrogenase(ALDH)were measured.Results The combination of cefoperazone and ethanol increased the maximum plasma concentration of ethanol and led to the accumulation of acetaldehyde in the blood.After 0 days and 3 days of cefoperazone administration,inhibition of hepatic ALDH activity could be detected.Ceftazidime had no significant effects on the metabolism of ethanol and acetaldehyde.Moreover,the activities of hepatic ADH and ALDH were not significantly changed after ceftazidime treatment.Conclusion Based on the data of ethanol and acetaldehyde metabolism in the blood of rats that consumed alcohol after administration of cefoperazone or ceftazidime,as well as the observed changes in hepatic ADH and ALDH activities,it can be concluded that the DLR induced by cefoperazone is mainly due to ALDH inhibition in the liver,whereas ceftazidime does not have similar effects.When combined with ethanol,cephalosporins with different structures induce DLR by distinct mechanisms.
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