[Free methyltetrazolethiol concentrations in men subjected to intravenous administration of cephems with methyltetrazolethiol].
The disulfiram-like reaction due to cephems with methyltetrazolethiol (tetrazole) moiety was studied in biotransformation of these drugs. The serum tetrazole concentration was determined following intravenous administration of cefoperazone (CPZ) 1 g, latamoxef (LMOX) 1 g, or cefmetazole (CMZ) 2 g to patients suffering infections without liver dysfunction, and of CPZ 1 g to patients with liver cirrhosis. Tetrazole concentrations in normal patients were 0.5-2.0 micrograms/ml after 3 hours, and 0.14-0.26 micrograms/ml after 12 hours, and undetectable after 24 hours. On the other hand, the tetrazole concentration in cirrhotic patients was 0.143 +/- 0.07 micrograms/ml (mean +/- SD) even after 24 hours. Therefore, it is concluded that the disulfiram-like reaction due to cephems with tetrazole moiety closely related to the metabolism of these drugs in liver, and probably be caused by the inhibition of acetaldehyde dehydrogenase activity in liver by the free tetrazole group produced by the metabolism of these drugs in liver.
D000445:Aldehyde Oxidoreductases / Q000037:antagonists & inhibitors; D001393:Azoles / Q000097:blood*; D001711:Biotransformation; D015311:Cefmetazole; D002438:Cefoperazone / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D002511:Cephalosporins / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D002513:Cephamycins / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D004221:Disulfiram / Q000494:pharmacology; D006801:Humans; D007275:Injections, Intravenous; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008103:Liver Cirrhosis / Q000378:metabolism; D008875:Middle Aged; D009070:Moxalactam / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D013777:Tetrazoles / Q000097:blood*
D001393:Azoles; D002511:Cephalosporins; D002513:Cephamycins; D013777:Tetrazoles; C038625:1-N-methyl-5-thiotetrazole; D015311:Cefmetazole; D002438:Cefoperazone; D000445:Aldehyde Oxidoreductases; C018699:aldehyde dehydrogenase (NAD(P)+); D004221:Disulfiram; D009070:Moxalactam