Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1 Pharmacodynamic properties
Pharmacotherapeutic group: ophthalmologicals, anti-infectives
ATC code: S01AE01

Mechanism of action
The derivative of quinolinic acid, ofloxacin, is a gyrase inhibitor with bactericidal effect.

Breakpoints
In the resistance study mentioned below, ofloxacin was tested using the commonly applied dilution series. The following minimum inhibitory concentrations (MICs) have been determined for susceptible and resistant agents.

EUCAST (European Committee on Antimicrobial Susceptibility Testing) breakpoints: Agent                               Susceptible            Resistant
Enterobacteriaceae                  ≤0.5 mg/1              >1 mg/1
Staphylococcus spp.                 ≤1 mg/1                >1 mg/1
Streptococcus pneumoniae            ≤0.125 mg/1            >4 mg/1
Haemophilus influenzae              ≤0.5 mg/1              >0.5 mg/1 Moraxella catarrhalis               ≤0.5 mg/1              >0.5 mg/1 Neisseria gonorrhoeae               ≤0.12 mg/1             >0.25 mg/1 No species-specific breakpoints *   ≤0.5 mg/1              >1 mg/1
* Primarily based on serum pharmacokinetics

Antibacterial spectrum
The antibacterial spectrum of ofloxacin includes fastidious anaerobes, facultative anaerobes, aerobes and other germs, such as, for example, chlamydia.
The prevalence of acquired resistance may vary geographically and with time for selected species and local information on resistance is desirable, particularly when treating severe infections. If necessary, expert advice should be sought when the local prevalence of resistance is such that the utility of ofloxacin in infections is questionable.
Especially in severe infections or lack of efficacy a microbiological diagnosis with detection of the pathological germ and its sensitivity to ofloxacin should be done. A cross resistance of ofloxacin with other fluoroquinolones may occur.

Resistance data presented in the table below are mainly based on current results of a study on the prevalence of resistance among 1391 bacterial isolates obtained from patients with eye infections (predominantly external smears) in 31 German centres. Data are based on the above breakpoints for systemic use. Topical application of ofloxacin to the eye usually achieves much higher antibiotic concentrations in the anterior eye segment than by systemic route. Therefore, clinical efficacy for approved indications may also be achieved with agents, such as.
B. Enterococcus spp., being defined as resistant in the in vitro resistance determination.

Commonly susceptible species

Aerobic Gram-positive-microorganisms
Bacillus spp.
Staphylococcus aureus (methicillin-susceptible)
Aerobic Gram-negative microorganisms
Acinetobacter baumannii
Acinetobacter lwoffi
Enterobacter cloacae
Escherichia coli
Haemophilus influenzae
Haemophilus parainfluenzae
Klebsiella oxytoca
Klebsiella pneumoniae
Moraxella catarrhalis
Proteus mirabilis
Serratia marcescens

Species for which acquired resistance may pose a problem during treatment 
Aerobic Gram-positive microorganisms
Corynebacterium spp.
Enterococcus faecalis
Staphylococcus aureus (methicillin-susceptible) +
Staphylococcus epidermidis
Streptococcus pneumoniae $
Streptococci (except Streptococcus pneumoniae) $

Aerobic Gram-negative microorganisms
Pseudomonas aeruginosa
Stenotrophomonas maltophilia
Inherently resistant species

Aerobic Gram-positive microorganisms
Enterococcus spp.

$
The natural susceptibility of most bacterial isolates to a given antibiotic is said to be intermediate. However, concentrations of at least 4 mg/l have been seen in the tear film for four hours following a single application, which reliably kills 100% of the isolates.
+ In at least one area, the resistance rate is over 50%.

Pharmacokinetic Properties

5.2 Pharmacokinetic properties

The efficacy primarily depends on the ratio of maximum tissue concentration (Cmax) and minimal inhibitory concentration (MIC) of the pathogen.

Non-clinical studies revealed evidence that ofloxacin applied topically has been detected in the cornea, conjunctiva, eye muscle, sclera, iris, ciliary body and anterior chamber. Repeated application also led to therapeutic concentrations in the vitreous.
Following a single dosing of ointment strip with length of approx. 1 cm (equivalent to 0.12 mg ofloxacin), concentrations of 9.72 μg/g in the cornea and 1.61 μg/g in the sclera reached maximum levels five minutes post-dose. Concentration values then decreased slowly. Aqueous humour and corneal concentrations measured maximum levels of 0.69 μg/g and 4.87μg/g one hour post-dose.