1-n-methyl-5-thiotetrazole and Respiratory-Tract-Infections

During the period February 1980-March 1982, clinical evaluation was carried out on 23,855 cases given cefmetazole (CMZ) in 3,916 medical treatment centres in Japan. The drug was found to have superior efficacy and to be of value for all age groups, ranging from infants and small children to the elderly, in infections due to Gram-positive cocci, Gram-negative bacilli and anaerobic bacteria sensitive to this drug. Experiments were also conducted to elucidate the mechanism of development of the disulfiram-like reaction found in cephems with a methyltetrazolylthiomethyl group at the 3 position, i.e., cefmetozole (CMZ), cefoperazone (CPZ) and latamoxef (LMOX). These experiments provided clear evidence that the reaction is due to a rise in the blood concentration of acetaldehyde, as a result of inhibition of acetaldehyde dehydrogenase activity caused by these cephems. The extent of increase in the blood concentration of AcH is proportional to the urinary excretion rate of mercaptomethyltetrazole (Me-TZ), being in the order CPZ greater than LMOX greater than CMZ. This order is believed to be due to the extent of distribution in bile by various antibiotics and to their stability in the tissue fluids.

Topics: Adolescent; Adult; Aged; Aging; Aldehyde Oxidoreductases; Animals; Azoles; Bacterial Infections; Cefmetazole; Cefoperazone; Cephamycins; Child; Child, Preschool; Chromatography, High Pressure Liquid; Dogs; Drug Evaluation; Ethanol; Humans; In Vitro Techniques; Infant; Japan; Macaca fascicularis; Male; Middle Aged; Moxalactam; Rats; Rats, Inbred Strains; Respiratory Tract Infections; Structure-Activity Relationship; Tetrazoles