CEPHEM ANTIBIOTICS AND ALCOHOL METABOLISM .1. DISULFIRAM-LIKE REACTION RESULTING FROM INTRAVENOUS ADMINISTRATION OF CEPHEM ANTIBIOTICS

Abstract

Doses of 50-500 mg/kg of the cephem antibiotics were injected i.v. to male rats twice/day for 3 days. After the last injection, the rats were fasted for 17 h and then orally administered 2 g/kg of 20% ethanol. The blood levels of ethanol and acetaldehyde (AcH) were determined by gas chromatography. Cefotiam, cefsulodin and cefazolin did not affect the blood levels of ethanol and AcH as compared with those of the control. Cefmetazole, cefamandole and cefoperazone did not change the blood ethanol level, but these antibiotics increased the blood AcH level dose-dependently. Cefamandole was especially able to sustain a high blood AcH level for over 8 h. All of the antibiotics which increased blood AcH levels contain the 1-methyl-1H-tetrazole-5-thiol (TZ) group in their chemical structure. I.v. injection of TZ caused a significant increase of the blood AcH level without influence on the blood ethanol level. 1-(2-Dimethylaminoethyl)-1H-tetrazole-5-thiol (MTZ), the functional group which is contained in cefotiam, did not affect the blood levels of ethanol and AcH. Apparently the disulfiram-like reaction of cefmetazole, cefamandole and cefoperazone results from an increase of the blood AcH level, and the 3-substituent group in aminocephalosporanic acid, i.e., TZ, is an important factor for the reaction.