Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1   Pharmacodynamic properties
Pharmacotherapeutic group: Ophthalmologicals; anti-infectives, other anti-infectives, ATC code: S01AE07

Mechanism of Action:
Moxifloxacin, a fourth-generation fluoroquinolone, inhibits the DNA gyrase and topoisomerase IV required for bacterial DNA replication, repair, and recombination.

Resistance:
Resistance to fluoroquinolones, including moxifloxacin generally occurs by chromosomal mutations in genes encoding DNA gyrase and topoisomerase IV. In Gram-negative bacteria, moxifloxacin resistance can be due to mutations in mar (multiple antibiotic resistance) and the qnr (quinolone resistance) gene systems. Resistance is also associated with expression of bacteria efflux proteins and inactivating enzymes. Cross-resistance with beta-lactams, macrolides and aminoglycosides is not expected due to differences in mode of action.

Susceptibility Testing Breakpoints:
There are no pharmacological data correlated with clinical outcome for moxifloxacin administered as a topical agent. As a result, the European Committee on Antimicrobial Susceptibility Testing (EUCAST) suggests the following epidemiological cut-off values (ECOFF mg/l) derived from MIC distribution curves to indicate susceptibility to topical moxifloxacin:

Corynebacterium                  ND
Staphylococcus aureus            0.25 mg/l
Staphylococcus, coag-neg.        0.25 mg/l
Streptococcus pneumoniae         0.5 mg/l
Streptococcus pyogenes           0.5 mg/l
Streptococcus, viridans group    0.5 mg/l
Enterobacter spp.                0.25 mg/l
Haemophilus influenzae           0.125 mg/l
Klebsiella spp.                  0.25 mg/l
Moraxella catarrhalis            0.25 mg/l
Morganella morganii              0.25 mg/l
Neisseria gonorrhoeae            0.032 mg/l
Pseudomonas aeruginosa           4 mg/l
Serratia marcescens              1 mg/l

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. As necessary, expert advice should be sought when the local prevalence of resistance is such that the utility of moxifloxacin in at least some types of infections is questionable.

COMMONLY SUSCEPTIBLE SPECIES
Aerobic Gram-positive micro-organisms:
Corynebacterium species including
Corynebacterium diphtheriae
Staphylococcus aureus (methicillin susceptible)
Streptococcus pneumoniae
Streptococcus pyogenes
Streptococcus viridans Group
Aerobic Gram-negative micro-organisms:
Enterobacter cloacae
Haemophilus influenzae
Klebsiella oxytoca
Moraxella catarrhalis
Serratia marcescens
Anaerobic micro-organisms:
Proprionibacterium acnes
Other micro-organisms:
Chlamydia trachomatis

SPECIES FOR WHICH ACQUIRED RESISTANCE MAY BE A PROBLEM
Aerobic Gram-positive micro-organisms:
Staphylococcus aureus (methicillin resistant)
Staphylococcus, coagulase-negative species (methicillin resistant) Aerobic Gram-negative micro-organisms:
Neisseria gonorrhoeae
Other micro-organisms:
None

INHERENTLY RESISTANT ORGANISMS
Aerobic Gram-negative micro-organisms:
Pseudomonas aeruginosa
Other micro-organisms:
None

Pharmacokinetic Properties

5.2 Pharmacokinetic properties
Following topical ocular administration of VIGAMOX, moxifloxacin was absorbed into the systemic circulation. Plasma concentrations of moxifloxacin were measured in 21 male and female subjects who received bilateral topical ocular doses of VIGAMOX ophthalmic solution 3 times a day for 4 days. The mean steady-state Cmax and AUC were 2.7 ng/mL and 41.9 ng-hr/mL, respectively. These exposure values are approximately 1,600 and 1,200 times lower than the mean Cmax and AUC reported after therapeutic 400 mg oral doses of moxifloxacin. The plasma half-life of moxifloxacin was estimated to be 13 hours.