Evidence for impaired hepatic vitamin K1 metabolism in patients treated with N-methyl-thiotetrazole cephalosporins.
In 8 patients on no oral intake and with parenteral alimentation, administration of cephalosporins with N-methyl-thiotetrazole side chain (moxalactam, cefamandole), was associated with prolongation of prothrombin time, appearance in the circulation of descarboxy-prothrombin (counter immunoelectrophoresis and echis carinatus assay) and diminution of protein C. Acute administration of 10 mg vitamin K1 was followed by the transient appearance of vitamin K1 2,3-epoxide, indicating an impaired hepatocellular regeneration of vitamin K1 from the epoxide. Impaired hepatic vitamin K1 metabolism, tentatively ascribed to the N-methyl-thiotetrazole group, is one (but possibly not the only) cause of bleeding complications and depression of vitamin K1-dependent procoagulants in patients treated with the new class of cephalosporins.
D000368:Aged; D001779:Blood Coagulation Factors / Q000032:analysis; D002435:Cefamandole / Q000627:therapeutic use*; D005260:Female; D006023:Glycoproteins / Q000032:analysis; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008297:Male; D009070:Moxalactam / Q000627:therapeutic use*; D011486:Protein C; D011517:Prothrombin Time; D012141:Respiratory Tract Infections / Q000188:drug therapy; D014552:Urinary Tract Infections / Q000188:drug therapy; D010837:Vitamin K 1 / Q000031:analogs & derivatives / Q000032:analysis / Q000378:metabolism*
D001779:Blood Coagulation Factors; D006023:Glycoproteins; D011486:Protein C; C016186:vitamin K1 oxide; D002435:Cefamandole; D010837:Vitamin K 1; D009070:Moxalactam