EFFECTS OF CEPHEM ANTIBIOTICS ON ETHANOL-METABOLISM

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Abstract
Disulfiram-like reactions were reported in patients receiving cephem antibiotics which possess a mercaptomethyltetrazole (Me-TZ) side chain in their molecular structure. The relationship between the formation of Me-TZ and its inhibitory action on alcohol metabolism after treatment with the cephem antibiotics was investigated. 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 in the order of CPZ > LMOX .times. 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. 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 > LMOX > CMZ-treatment. There apparently are some differences in the disulfiram-like reactions among animal species and antibiotics, which can be attributed to the intrinsic distribution and stability of each of the antibiotics in the body.