CEPHEM ANTIBIOTICS AND ALCOHOL METABOLISM
1985 年 38 巻 3 号 p. 634-642
詳細
1985 年 38 巻 3 号 p. 634-642
Mechanisms of the disulfiram-like reaction of cephem antibiotics were studied. Changes in ethanol (EtOH) and acetaldehyde (AcH) levels in the blood with EtOH loading following daily intravenous administration of cephem antibiotics were determined in rats and the followings were found:
1. The daily intravenous injection of cefazolin, cefotiam (CTM), cefsulodin, cefoxitin or ceftizoxime in no way varied the changes in the EtOH and AcH levels in the blood with EtOH loading.
2. The daily intravenous injection of cefmetazole, cefoperazone, cefamandole, latamoxef, cefmenoxime or cefotetan caused the AcH level in the blood to be elevated significantly until at least 8 hours after the EtOH loading, but was inert on the EtOH level on the blood.
3. The daily administration of 1-methyl-2-tetrazoline-5-thione (TZ), a compound having a partial structure similar to those of the cephem antibiotics elevating the AcH level in the blood on EtOH loading, was inert on the EtOH level in the blood but elevated the AcH level in the blood. The daily administration of 1-(2-dimethylaminoethyl)-2-tetrazoline-5-thione (MTZ), a compound having a partial structure similar to that of CTM, was inert either on the EtOH or AcH level in the blood.
4. The cephem antibiotics elevating the AcH level in the blood all had a (1-methy1-1H-tetrazol-5-yl) thiomethyl group in the 3 position of the aminocephalosporanic acid nucleus.
5. It was though that the disulfiram-like reaction caused by the cephem antibiotics was derived from the elevation of AcH level in the blood.
6. The disulfiram-like reaction was presumed to take place through the mechanism that the antibiotics, when injected intravenously, might be excreted into the bile to be metabolized in the intestinal tract, where they might release TZ, which in turn might inhibit aldehyde dehydrogenase.
7. The patient on treatment with or not more than 7 days after treatment with the cephem antibiotics causative of this phenomenon should refrain from the ingestion of alcohol-containing liquor.
