• Lowest LEVAQUIN Prices Online
• FREE Doctor Consultation
• Security and Confidentiality
• NO Hidden Fees
• Add to favorites

Pharmacokinetics

The mean (±SD) pharmacokinetic parameters of levofloxacin determined under single and steady state conditions following oral (p.o.) or intravenous (IV) doses of levofloxacin are summarized in TABLE 9A and TABLE 9B.

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 inhibition of DNA gyrase (bacterial topolsomerase II), an enzyme required for DNA raplication, transcription, repair and recombination.

Levofloxacin has in vitro activity against a wide range of gram-negative and gram-positive microorganisms. Levofloxacin is often bactericidal at concentrations equal to or slightly greater than inhibitory concentrations.

Fluoroquinolones differ in chemical structure and mode of action from b-lactam antibiotics. Fluoroquinolones may, therefore, be active against bacteria resistant to b-lactam antibiotics.

Resistance to levofloxacin due to spontaneous mutation in vitro is a rate occurrence (range: 10-8 to 10-10). Although cross-resistance has been observed between levofloxacin and some other fluoroquinolones, some microorganisms resistant to other fluoroquinolones may be susceptible to levofloxacin.

Levofloxacin has been shown to be active against most strains of the following microorganisms both in vitro and in clinical infections as described in INDICATIONS AND USAGE:

Aerobic gram-positive microorganisms

Enterococcus faecalis
Staphylococcus aureus
Streptococcus pneumonia
Streptococcus pyogenes

Aerobic gram-negative microorganisms

Enterobacter cloacae
Escherichia coli
Haemophilus influenzae
Haemophilus parainfluenzae
Klebsiella pneumoniae
Legionella pneumophila
Moraxella caterrhalis
Proteus mirabilis
Pseudomonas aeruginosa

As with other drugs in this class, some strains of Pseudomonas aeruginosa may develop resistance fairly rapidly during treatment with levofloxacin.

Other microorganisms

Chlamydia pneumoniae
Mycoplasma pneumoniae

The following in vitro data are available, but their clinical significance is unknown.
Levofloxacin exhibits in vitro minimum inhibitory concentrations (MICs) of 2mcg/ml or less against most strains of the following microorganisms: however, the safety and effectiveness of levofloxacin in treating clinical infections due to those microorganisms have not been established in adequate and well-controlled trials.

CLINICAL STUDIES
Community-Acquired Bacterial Pneumonia: Adult inpatients and outpatients with a diagnosis of community-acquired bacterial pneumonia were evaluated in two pivotal clinical studies. In the first study, 590 patients were enrolled in a prospective, multi-center, unblinded randomized trial comparing levofloxacin 500 mg once daily orally or intravenously for 7 to 14 days to ceftriaxone 1 to 2 grams intravenously once or in equally divided doses twice daily followed by cefuroxime axetil 500 mg orally twice daily for a total of 7 to 14 days. Patients assigned to treatment with the control regimen were allowed to receive erythromycin (or doxycycline if intolerant of erythromycin) in an infection due to atypical pathogens was suspected or proven. Clinical and microbiologic evaluations were performed during treatment, 5 to 7 days posttherapy, and 3 to 4 weeks posttherapy. Clinical success (cure plus improvement) with levofloxacin at 5 to 7 days posttherapy, the primary efficacy variable in this study, was superior (95%) to the control group (83%) [95% Cl of -19,-6]. In the second study, 264 patients were enrolled in a prospective, multi-center, noncomparative trial of 500 mg levofloxacin administered orally or intravenously once daily for 7 to 14 days. Clinical success for clinically evaluable patients was 93%. For both studies, the clinical success rate in patients with atypical pneumonia due to Chlarnydia pneumoniae, Mycoplasma pneumoniae, and Legionella pneumophila were 96%, 96%, and 70%, respectively.

ANIMAL PHARMACOLOGY
Levofloxacin and other quinolones have been shown to cause arthropathy in immature animals of most species tested. (See WARNINGS.) In immature dogs (4-5 months old), oral doses of 10 mg/kg/day for 7 days and intravenous doses of 4 mg/kg/day for 14 days of levofloxacin resulted in arthropathic lesions. Administration at oral doses of 300 mg/kg/day for 7 days and intravenous doses of 60 mg/kg/day for 4 weeks produced arthropathy in juvenile rats.

When tested in a mouse ear swelling bioassay, levofloxacin exhibited phototoxicity similar in magnitude to ofloxacin, but less phototoxicity than other quinolones.

While crystalluria has been observed in some intravenous rat studies, urinary crystals are not formed in the bladder, being present only after micturition and are not associated with nephrotoxicity.

In mice, the CNS stimulatory effect of quinolones is enhanced by concomitant administration of non-steroidal and anti-inflammatory drugs.

In dogs, levofloxacin administered at 6 mg/kg/day or higher by rapid intravenous injection produced hypotensive effects. These effects were considered to be related to histamine release.

In vitro and in vivo studies in animals indicate that levofloxacin is neither an enzyme inducer or inhibitor in the human therapeutic plasma concentration range; therefore, no drug metabolizing enzyme-related interactions with other drugs or agents are anticipated.

<< BACK