Effect of N-methyl-thiotetrazole on vitamin K epoxide reductase.
Clinical use of antibiotics containing a N-methyl-thiotetrazole (NMTT) side chain has been reported to be associated with an increased incidence of a vitamin K-responsive hypoprothrombinemia. Administration of NMTT to rats decreased the activity of the liver microsomal vitamin K epoxide reductase, increased the liver ratio of vitamin K epoxide to vitamin K, and decreased the rate of metabolism of injected vitamin K epoxide. These responses are the same as those observed following the administration of coumarin anticoagulants. In contrast to the effect of coumarin anticoagulants, NMTT did not inhibit the vitamin K epoxide reductase in vitro. These data suggest that the hypoprothrombinemia which has been observed following use of these antibiotics results from the inactivation of the liver vitamin K epoxide reductase by NMTT or a NMTT metabolite.
D000818:Animals; D001393:Azoles / Q000494:pharmacology*; D003374:Coumarins / Q000494:pharmacology; D003600:Cytosol / Q000201:enzymology; D004229:Dithiothreitol; D007020:Hypoprothrombinemias / Q000139:chemically induced / Q000209:etiology; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D013777:Tetrazoles / Q000494:pharmacology*; D014812:Vitamin K / Q000378:metabolism; D010837:Vitamin K 1 / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000378:metabolism; D064417:Vitamin K Epoxide Reductases; D014859:Warfarin / Q000494:pharmacology
D001393:Azoles; D003374:Coumarins; D013777:Tetrazoles; D014812:Vitamin K; C038625:1-N-methyl-5-thiotetrazole; C016186:vitamin K1 oxide; D014859:Warfarin; D010837:Vitamin K 1; C030123:coumarin; D006899:Mixed Function Oxygenases; D064417:Vitamin K Epoxide Reductases; D004229:Dithiothreitol