Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1        Pharmacodynamic properties
Pharmacotherapeutic group: Ophthalmologicals, anti-infectives, fluoroquinolones 
ATC code: S01AE01.

Ofloxacin is a synthetic fluorinated 4-quinolone, having fast acting, broad spectrum bactericidal activity against certain aerobic gram-positive and gram- negative bacteria.

Ofloxacin has been shown to be active against most strains of the following organisms both in vitro and clinically in ophthalmic infections. Clinical trial evidence of the efficacy of OFLOX against S. pneumoniae was based on a limited number of isolates.

Gram-negative bacteria: Acinetobacter calcoaceticus var. anitratum and A.
calcoaceticus var. lwoffi; Enterobacter sp. including E. cloacea, Haemophilus sp.
including H. influenza and H. aegyptius; Klebsiella sp. including K. pneumoniae; Moraxella sp; Morganella morganii; proteus sp. including P. mirabilis; Pseudomonas sp. including P. aeruginosa, P. cepacia, and P. fluoroscens; and Serrata sp. including S. marcescens.

Gram-positive bacteria: Bacillus sp; Corynebacterium sp; Micrococcus sp; Staphylococcus sp. including S. aureus and S. epidermidis; Streptococcus sp. including S. pneumoniae (see above), S. viridans and beta-haemolytic Streptococcus.

Ofloxacin appears to have more than one mechanism contributing to its bactericidal action. The primary mechanism of action is believed to be the inhibition of bactericidal DNA gyrase, the enzyme responsible for inserting negative supercoils into bacterial DNA. This inhibition causes the rapid death of bacteria by stopping DNA replication, which apparently induces a cellular response leading to further damage to bacterial DNA and preventing normal gene expression. In addition, ofloxacin possesses an additional bactericidal mechanism which is independent of protein and DNA synthesis. Therefore it is bactericidal in both the replicating and non-replicating stages of growth. Mammalian cells are not inhibited by the quinolones.

Pharmacokinetic Properties

5.2        Pharmacokinetic Properties

After ophthalmic instillation as an eyedrop, ofloxacin is well absorbed and distributed to all parts of the eye.

In a healthy volunteer study, mean tear film concentrations of ofloxacin measured four hours after topical dosing (9.2 mcg/ml were higher than the 2 mcg/ml) minimum concentration of ofloxacin necessary to inhibit 90% of most ocular bacterial strains (MIC 90) in vitro.

Systemically absorbed ofloxacin is widely distributed and undergoes rapid elimination from the body. It is mainly excreted unchanged in the urine.
The maximal serum concentration observed after ophthalmic doses to man (approx.1.9 ng/ml) was at least two thousand fold lower than that after an oral 300 mg dose (approx.
4625 ng/ml).

Ofloxacin is not subject to degradation by beta-lactamase enzymes nor is it modified by enzymes such as aminoglycoside adenylases or phosphorylases, or chloramphenicol acetyltransferase.