Summary
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 (<0.030 µg/ml). The K1-epoxide concentrations found in our three patients treated with cephalosporins were 0.12, 0.16 and 0.19 µg/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.
Abbreviations
- PT:
-
prothrombin time
- TT:
-
thrombin time
- PTT:
-
partial thromboplastin time
- PC:
-
platelet count
- ICU:
-
intensive care unit
- EEG:
-
electroencephalogram
- K1-epoxide:
-
vitamin K1 2,3-epoxide
References
Editorial (1981) Information on adverse reactions to drugs (58): deficiency due to antibiotics. Jap Med Gaz Sept 20:12
Bruch K (1983) Hypoprothrombinaemia and cephalosporins. Lancet i:535–536
Lipsky JJ (1983) N-methyl-thio-tetrazole inhibition of the gamma carboxylation of glutamic acid: possible mechanism for antibiotic-associated hypoprothrombinaemia. Lancet ii:192–193
Lipsky JJ (1983) Latamoxef-associated hypoprothrombinaemia. Lancet ii:624
Schwigon CD, Barkow D (1982) Blutgerinnungsstörungen unter Cefaperazon und Lamoxactam. Diagnostik Intensivther 7:221–225
Bechtold H, Klein F, Trenk D, Jähnchen E (1984) Improved method for quantitative analysis of vitamin K1 and vitamin K1 2,3-epoxide in human plasma by electron-capture gasliquid capillary chromatography. J Chromatogr 306:333–337
Bechtold H, Trenk D, Jähnchen E, Meinertz T (1983) Plasma vitamin K1 2,3-epoxide as diagnostic aid to detect surreptitious ingestion of oral anticoagulant drugs. Lancet i:595–597
Bechtold H, Trenk D, Meinertz T, Rowland M, Jähnchen E (1983) Cyclic interconversion of vitamin K1 and vitamin K1 2,3-epoxide in man. Br J Clin Pharmacol 16:683–689
Bell RG (1978) Metabolism of vitamin K and prothrombin synthesis: anticoagulants and the vitamin K-epoxide cycle. Fed Proc 37:2599–2604
Shearer M, McBurney A, Breckenridge A, Barkhan P (1977) Effect of warfarin on the metabolism of phylloquinone (vitamin K1): Dose-response relationship in man. Clin Sci Mol Med 52:621–630
Bjornsson TD, Meffin RJ, Swezey SE, Blaschke TF (1979) Effects of clofibrate and warfarin alone and in combination on the disposition of vitamin K1. J Pharmacol Exp Ther 210:322–326
Park BK, Leck JB (1981) On the mechanism of salicylate-induced hypoprothrombinaemia. J Pharm Pharmacol 1981; 33:25–28
Hildebrandt EF, Suttie JW. The effects of salicylate on enzymes of vitamin K metabolism. J Pharm Pharmacol 35:421–426
Jähnchen E, Bechtold H, Klein F, Reinecke J, Trenk D, Meinertz T (1983) On the mechanism of salicylate induced hypoprothrombinaemia in man. Circulation 68 (suppl III):266
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Bechtold, H., Lorenz, J., Weilemann, L.S. et al. Possible coumarin-like mechanism of action for cephalosporins. Klin Wochenschr 62, 885–886 (1984). https://doi.org/10.1007/BF01712009
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/BF01712009