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Flomoxef, a new oxacephem antibiotic, does not cause hemostatic defects
M Cazzola1, V Brancaccio, C De Giglio
1Institute of Pharmacology and Toxicology, Medical School, Secomo University, Naples, Italy.
Abstract:
Antibiotics of the beta-lactam class may cause coagulation defects and bleeding. It has been suggested that N-methyltetrazolethiol (NMTT), a common side chain group at the 3'-position of the cephem or 1-oxacephem frame, could be responsible for the hypoprothrombinemic effect of the antibiotics and that it could inhibit the liver vitamin K-epoxide reductase activity. Flomoxef (6315-S) is a new oxacephem antibiotic which differs from latamoxef because it has [1-(2-hydroxethyl)-1H-tetrazol-5-yl] thiomethyl (HTT) as a side chain at the 3'-position of cephem group instead of NMTT and an extensive modification of 7 beta-acylamino side chain. The present study was carried out to study its effects on vitamin K-dependent blood coagulation parameters in human volunteers. Ten adult patients (6 men and 4 women), suffering from chronic bronchitis, entered into the study. Each patient received ten 1 g i.m. injections of flomoxef at 12-hourly intervals. Apparently, the treatment with this oxacephem antibiotic had no significant effect. PT, PTT and fibrinogen remained in the normal range in all patients and factors II+VII+X, protein C, protein S and AT III were not depleted. The trend was similar both in men and women. Based on the results of the present study, we conclude that flomoxef is an antibiotic that does not exhibit an effect on blood coagulation, even in males.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Flomoxef, a new oxacephem antibiotic, was evaluated for its effects on blood coagulation. The study found no significant impact on vitamin K-dependent coagulation parameters in human volunteers, indicating it does not cause bleeding risks.
Area of Science:
- Pharmacology
- Clinical Medicine
- Hematology
Background:
- Beta-lactam antibiotics can cause bleeding due to coagulation defects.
- N-methyltetrazolethiol (NMTT) side chain is suspected to inhibit vitamin K-epoxide reductase, leading to hypoprothrombinemia.
- Flomoxef, a novel oxacephem, features a different side chain ([1-(2-hydroxethyl)-1H-tetrazol-5-yl] thiomethyl - HTT) and modified acylamino side chain.
Purpose of the Study:
- To investigate the effects of flomoxef on vitamin K-dependent blood coagulation parameters.
- To assess the safety of flomoxef concerning bleeding risks in human volunteers.
Main Methods:
- Ten adult patients with chronic bronchitis received ten 1g intramuscular injections of flomoxef every 12 hours.
- Prothrombin time (PT), partial thromboplastin time (PTT), fibrinogen levels, and coagulation factors (II+VII+X, protein C, protein S, AT III) were monitored.
Main Results:
- Flomoxef treatment showed no significant effect on PT, PTT, and fibrinogen levels.
- No depletion of coagulation factors II+VII+X, protein C, protein S, and AT III was observed.
- The observed trend was consistent across both male and female participants.
Conclusions:
- Flomoxef does not appear to affect blood coagulation parameters.
- The novel oxacephem antibiotic flomoxef is unlikely to pose a risk of bleeding or hypoprothrombinemia.
- Clinical use of flomoxef is deemed safe concerning its impact on hemostasis.