Studies on oxacephem antibiotics: comparison of the effects of 1-oxa and 1-thia cephalosporins on blood coagulation activities and vitamin K metabolism in rats.
Oxacephem antibiotics have been developed to increase the antibacterial activity of cephem antibiotics, but the effect of 1-oxygen replacement of cephem antibiotics on blood coagulation activities is not yet known. Therefore, latamoxef (LMOX), flomoxef (FMOX) and their 1-S congeners were examined for their effects on prothrombin time, activated partial thromboplastin time, plasma prothrombin and Factor VII levels, plasma and liver descarboxyprothrombin (PIVKA-II) levels, and liver microsomal vitamin K epoxide reductase activities in rats kept on a vitamin K-deficient diet. Under the vitamin-deficient states, LMOX, FMOX and their 1-S congeners inhibited the vitamin K epoxide reductase, although the effect of FMOX or its congener was much less than that of LMOX, and they decreased the blood clotting activities in rats fed a vitamin K-deficient diet. However, no difference was found in these effects between LMOX and its 1-S congener or between FMOX and its 1-S congener. This result suggests that the 1-oxygen replacement of cephem antibiotics is not responsible for the hypoprothrombinemic effect of the antibiotics.
Shionogi Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
K
K
Uchida
T
T
Matsubara
K
K
Hirauchi
D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects*; D002511:Cephalosporins / Q000494:pharmacology*; D005167:Factor VII / Q000032:analysis; D005340:Fibrinogen / Q000378:metabolism; D008297:Male; D009070:Moxalactam / Q000494:pharmacology; D010314:Partial Thromboplastin Time; D010974:Platelet Aggregation / Q000187:drug effects; D011517:Prothrombin Time; D051381:Rats; D011919:Rats, Inbred Strains; D014812:Vitamin K / Q000378:metabolism*; D014813:Vitamin K Deficiency / Q000097:blood / Q000378:metabolism
D002511:Cephalosporins; D014812:Vitamin K; D005167:Factor VII; D005340:Fibrinogen; C045693:flomoxef; D009070:Moxalactam