The effect of
flomoxef, a newly developed oxacephem
antibiotic with an N-hydroxyethyltetrazolethiol (HTT) side chain, on blood coagulation and alcohol metabolism was compared with that of a series of
cephalosporin antibiotics with
N-methyltetrazolethiol (NMTT), thiadiazolethiol (TDT) or methylthiadiazolethiol (MTDT) side chains in position 3' of the
cephalosporin nucleus known to cause
hypoprothrombinemia and
bleeding in patients who are malnourished, debilitated and/or of high age. A
disulfiram-like effect caused by inhibition of
aldehyde dehydrogenase was observed for NMTT-containing
antibiotics. Studies were carried out on healthy volunteers and on rats. Eight-day treatment with 2 g
flomoxef i.v. once or twice daily in five and six healthy male volunteers, respectively, did not cause any significant changes in prothrombin time (PT),
coagulation factors II, VII, IX or X, in
hepaplastin values or
fibrinogen levels, activated partial thromboplastin time (APTT), platelet counts, bleeding time, or
collagen- and
ADP-induced platelet aggregation. Inhibition of
vitamin K epoxide reductase was observed in rats treated with
flomoxef, yet to a much lesser extent than observed for
cephalosporins with NMTT, TDT or MTDT side chains. This defect was quickly normalized by
vitamin K injection. There were no differences between oxacephem (1-O) and cephem (1-S) compounds with respect to effects on blood clotting and platelet aggregation.
Flomoxef and its side chain HTT showed no influence on alcohol metbolism.