A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Quixin Pharmacology, Pharmacokinetics, Studies, Metabolism - Levofloxacin
Quixin Pharmacology, Pharmacokinetics, Studies, Metabolism - Levofloxacin
CLINICAL PHARMACOLOGY
Pharmacokinetics:
Levofloxacin concentration in plasma was measured in 15 healthy adult volunteers
at various time points during a 15-day course of treatment with QUIXIN™ solution.
The mean levofloxacin concentration in plasma 1 hour postdose, ranged from 0.86
ng/mL on Day 1 to 2.05 ng/mL on Day 15. The highest maximum mean levofloxacin
concentration of 2.25 ng/mL was measured on Day 4 following 2 days of dosing
every 2 hours for a total of 8 doses per day. Maximum mean levofloxacin concentrations
increased from 0.94 ng/mL on Day 1 to 2.15 ng/mL on Day 15, which is more than
1,000 times lower than those reported after standard oral doses of levofloxacin.
Levofloxacin concentration in tears was measured in 30 healthy adult volunteers
at various time points following instillation of a single drop of QUIXIN™ solution.
Mean levofloxacin concentrations in tears ranged from 34.9 to 221.1 µg/mL during
the 60-minute period following the single dose. The mean tear concentrations
measured 4 and 6 hours postdose were 17.0 and 6.6 µg/mL. The clinical significance
of these concentrations is unknown.
Microbiology:
Levofloxacin is the L-isomer of the racemate, ofloxacin, a quinolone antimicrobial
agent. The antibacterial activity of ofloxacin resides primarily in the L-isomer.
The mechanism of action of levofloxacin and other fluoroquinolone antimicrobials
involves the inhibition of bacterial topoisomerase IV and DNA gyrase (both of
which are type II topoisomerases), enzymes required for DNA replication, transcription,
repair, and recombination.
Levofloxacin has in vitro activity against a wide range of Gram-negative
and Gram-positive microorganisms and is often bactericidal at concentrations
equal to or slightly greater than inhibitory concentrations.
Fluoroquinolones, including levofloxacin, differ in chemical structure and
mode of action from (beta)-lactam antibiotics and aminoglycosides, and therefore
may be active against bacteria resistant to (beta)-lactam antibiotics and aminoglycosides.
Additionally, (beta)-lactam antibiotics and aminoglycosides may be active against
bacteria resistant to levofloxacin.
Resistance to levofloxacin due to spontaneous mutation in vitro is a
rare occurrence (range: 10 -9 to 10 -10 ).
Levofloxacin has been shown to be active against most strains of the following
microorganisms, both in vitro and in clinical infections as described
in the INDICATIONS AND USAGE section:
Aerobic Gram-positive microorganisms
Corynebacterium species*
Staphylococcus aureus (methicillin-susceptible strains only)
Staphylococcus epidermidis (methicillin-susceptible strains only)
Streptococcus pneumoniae
Streptococcus (Groups C/F)
Streptococcus (Group G)
Viridans group streptococci
Aerobic Gram-negative microorganisms
Acinetobacter lwoffii *
Haemophilus influenzae
Serratia marcescens *
*Efficacy for this organism was studied in fewer than 10 infections.
The following in vitro data are also available, but their clinical significance
in ophthalmic infections is unknown. The safety and effectiveness of levofloxacin
in treating ophthalmological infections due to these microorganisms have not
been established in adequate and well-controlled trials.
These organisms are considered susceptible when evaluated using systemic breakpoints.
However, a correlation between the in vitro systemic breakpoint and ophthalmological
efficacy has not been established. The list of organisms is provided as guidance
only in assessing the potential treatment of conjunctival infections. Levofloxacin
exhibits in vitro minimal inhibitory concentrations (MICs) of 2 µg/mL
or less (systemic susceptible breakpoint) against most (>=90%) strains of
the following ocular pathogens.
Aerobic Gram-positive microorganisms
Enterococcus faecalis
Staphylococcus saprophyticus
Streptococcus agalactiae
Streptococcus pyogenes
Aerobic Gram-negative microorganisms
Acinetobacter anitratus
Acinetobacter baumannii
Citrobacter diversus
Citrobacter freundii
Enterobacter aerogenes
Enterobacter agglomerans
Enterobacter cloacae
Escherichia coli
Haemophilus parainfluenzae
Klebsiella oxytoca
Klebsiella pneumoniae
Legionella pneumophila
Moraxella catarrhalis
Morganella morganii
Neisseria gonorrhoeae
Proteus mirabilis
Proteus vulgaris
Providencia rettgeri
Providencia stuartii
Pseudomonas aeruginosa
Pseudomonas fluorescens
Clinical Studies:
In randomized, double-masked, multicenter controlled clinical trials where
patients were dosed for 5 days, QUIXIN™ demonstrated clinical cures in 79% of
patients treated for bacterial conjunctivitis on the final study visit day (day
6-10). Microbial outcomes for the same clinical trials demonstrated an eradication
rate for presumed pathogens of 90%.
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