Fosmicin Mechanism of Action

Pharmacokinetics: Absorption and Excretion: In adult patients, IV injection of 1 g dissolved in 20 mL of 20% glucose solution produced a mean peak blood concentration of 74 mcg/mL at 30 min after injection which gradually declined to 8 mcg/mL by 6 hrs after injection. In healthy adult volunteers receiving 1-hr IV drip infusion of 2 g dissolved in 300 mL of 5% glucose solution, a mean peak blood concentration of 157.3 mcg/mL was attained at the time of completion of the infusion. This gradually decreased thereafter, approaching a level of 2.6 mcg/mL at 12 hrs after infusion.
The serum half-life was 1.8 hrs. The urinary recovery rate was 96% on an average within the first 2 hrs. It diffuses efficiently to the organs and tissues and is excreted in the urine in an active unchanged form.
Tissue Concentrations: In patients with respiratory tract infections, IV injection of 1 g produced a mean sputum concentration of 7 mcg/mL over the first 3 hrs after injection.
Distribution to the cerebrospinal fluid was observed in patients with meningitis after IV injection or continuous IV drip infusion.
In rabbits, good distribution to the kidney, liver, lung, pancreas, heart, spleen, thymus, aqueous humor, etc was confirmed.
Toxicology: Acute Toxicity: LD₅₀ of fosfomycin sodium (FOM-Na) (mg/kg): See Table 2.


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Subacute and Chronic Toxicities: Subacute toxicity tests revealed that the maximum nontoxic dose is 500 mg/kg/day in rats and 400 mg/kg/day in rabbits.
Chronic toxicity tests in rats and dogs indicated the maximum nontoxic dose to be 250 mg/kg/day for both animals.
Microbiology: The mode of action of fosfomycin is very unique. It is taken into bacterial cells in high concentration via the active transport system against a concentration gradient and inhibits the initial stage of cell wall synthesis (β-lactam antibiotics inhibit the final stage of cell wall synthesis).
Fosfomycin acts bactericidally on gram-positive and gram-negative pathogens. It is especially highly active against Pseudomonas aeruginosa, Proteus sp, Serratia marcescens and multidrug-resistant strains of Staphylococcus aureus and E. coli.
A synergistic effect has been reported between fosfomycin and other antibiotics eg, β-lactam antibiotics aminoglycosides, macrolide and tetracycline.
Teratogenicity: In animal studies, no adverse effects were observed in audiovisual or teratogenicity tests. No antigenicity of fosfomycin sodium has been found in experiments on the induction of IgG and IgE antibodies.
Fosfomycin has not been observed to show any antigenicity in animal studies.