[Effects of cephem antibiotics on ethanol metabolism]

Disulfiram-like reactions have been reported in patients receiving cephem antibiotics which possess a mercaptomethyltetrazole (Me-TZ) side chain in their molecular structure. The present study focused on the elucidation of the relationship between the formation of Me-TZ and its inhibitory action on alcohol metabolism after treatment with the cephem antibiotics. The cumulative urinary excretion of Me-TZ was determined in healthy volunteers and laboratory animals after i.v. administration of the cephem antibiotics: cefmetazole (CMZ), cefoperazone (CPZ) and latamoxef (LMOX). In humans, monkeys and rodents, the extent of urinary excretion of Me-TZ was found in the order of CPZ greater than LMOX greater than CMZ-treatment. To assess their influences on dehydrogenation of ethanol (EtOH) and acetaldehyde (AcH), rats and monkeys were treated with a single or multiple i.v. dose of Me-TZ and cephem antibiotics prior to the EtOH treatment. The blood EtOH levels were not affected with either the Me-TZ or the cephem pretreatments. On the contrary, the AcH levels were significantly elevated with each of the pretreatments. The dose response curves for AcH levels showed parallel lines corresponding to the urinary excretion of Me-TZ, i.e., CPZ greater than LMOX greater than CMZ-treatment. These results suggest that there are some differences in the disulfiram-like reactions among animal species and antibiotics, which will be attributed to the intrinsic distribution and stability of each of the antibiotics in the body.