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  • Title: [Cephem antibiotics and alcohol metabolism: (1) Disulfiram-like reaction resulting from intravenous administration of cephem antibiotics].
    Author: Yanagihara M, Okada K, Nozaki M, Tsurumi K, Fujimura H.
    Journal: Nihon Yakurigaku Zasshi; 1982 Jun; 79(6):551-60. PubMed ID: 6290355.
    Abstract:
    Fifty to 500 mg/kg doses of the cephem antibiotics were intravenously injected to male rats twice a day for 3 days. After the last injection, the rats were fasted for 17 hours and then orally administered 2 g/kg or 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 hours. All of the antibodies which increased blood AcH levels contain the 1-methyl-1H tetrazole-5-thiol (TZ) group in their chemical structure. Intravenous injection of TZ caused a significant increase of the blood AcH level without influence on the blood ethanol level. 1-(2-Dimethyl-aminoethyl 1H-tetrazole-5-thiol (MTZ), the functional group which is contained in cefotiam, did not affect the blood levels of ethanol and AcH. These results suggested that the disulfiram-like reaction of cefmetazole, cefamandole, and cefoperazone results from an increase of the blood AcH level, and the 3-substituent group in in aminocephalosporanic acid, i.e., TZ, is an important factor for the reaction.
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