title: Possible coumarin-like mechanism of action for cephalosporins.
abstract: In three patients treated with cephalosporins (one patient with latamoxef, two patients with cefazedone) vitamin K1 was injected to investigate whether this was followed by an increase in vitamin K1 2,3-epoxide plasma concentrations as compared to controls. Such a rise in K1-epoxide concentrations in the plasma can be demonstrated following treatment with coumarins. This reflects an inhibition of the vitamin K1-epoxide reductase in the liver. Coumarins are thought to induce hypoprothrombinaemia by such a mechanism. In all three patients we found a considerable increase in the vitamin K1-epoxide plasma concentrations following injection of 10 mg vitamin K1, whereas in normal subjects only traces of K1-epoxide could be detected (less than 0.030 micrograms/ml). The K1-epoxide concentrations found in our three patients treated with cephalosporins were 0.12, 0.16 and 0.19 micrograms/ml, respectively. This indicates that latamoxef or cefazedone might reduce clotting factor synthesis by a coumarin-like mechanism of action in these patients. Although the effect of cephalosporins in enhancing vitamin K1-epoxide plasma concentrations is less than that of coumarins, it might cause severe hypoprothrombinaemia in the presence of latent vitamin K deficiency.
mesh_terms: D000368:Aged; D002511:Cephalosporins / Q000009:adverse effects* / Q000494:pharmacology; D003374:Coumarins / Q000378:metabolism*; D005260:Female; D006801:Humans; D007020:Hypoprothrombinemias / Q000139:chemically induced; D008297:Male; D014812:Vitamin K / Q000097:blood / Q000378:metabolism
chemical_list: D002511:Cephalosporins; D003374:Coumarins; D014812:Vitamin K