Levixa Mechanism of Action

Pharmacology: Pharmacokinetics: Absorption: Levofloxacin is rapidly and almost completely absorbed after oral administration. Peak plasma concentrations are usually attained one to two hours after oral dosing. The absolute bioavailability of levofloxacin from a 500 mg tablet and a 750 mg tablet of levofloxacin are both approximately 99%, demonstrating complete oral absorption of levofloxacin.
Distribution: The mean volume of distribution of levofloxacin generally ranges from 74 to 112 L after single and multiple 500 mg or 750 mg doses, indicating widespread distribution into body tissues. Levofloxacin reaches its peak levels in skin tissues and in blister fluid of healthy subjects at approximately 3 hours after dosing. Levofloxacin also penetrates well into lung tissues. Lung tissue concentrations were generally 2- to 5-fold higher than plasma concentrations and ranged from approximately 2.4 to 11.3 mcg/g over a 24-hour period after a single 500 mg oral dose. Levofloxacin is mainly bound approximately 24 to 38% to serum albumin in humans.
Metabolism: Levofloxacin is stereochemically stable in plasma and urine and does not invert metabolically to its enantiomer, D-ofloxacin. Levofloxacin undergoes limited metabolism in humans and is primarily excreted as unchanged drug in the urine. Following oral administration, approximately 87% of an administered dose was recovered as unchanged drug in the urine. Following oral administration, approximately 87% of an administered dose was recovered as unchanged drug in urine within 48 hours, whereas less than 4% of the dose was recovered in feces in 72 hours. Less than 5% of an administered dose was recovered in the urine as the desmethyl and N-oxide metabolites, the only metabolites identified in humans. These metabolites have little relevant pharmacological activity.
Excretion: Levofloxacin is excreted largely as unchanged drug in the urine. The mean terminal plasma elimination half-life of levofloxacin ranges from approximately 6 to 8 hours following single or multiple doses of levofloxacin given orally or intravenously.
Microbiology: Mechanism of Action: The mechanism of action of levofloxacin and other fluoroquinolone antimicrobials involves inhibition of bacterial topoisomerase IV and DNA gyrase, enzymes required for DNA replication, transcription, repair and recombination.
Drug Resistance: Levofloxacin and other fluoroquinolones differ in chemical structure and mode of action from aminoglycosides, macrolides and beta-lactam antibiotics. Levofloxacin may, therefore, be active against bacteria resistant to these antimicrobials. Although cross-resistance has been observed between levofloxacin and some other fluoroquinolones, some microorganisms resistant to other fluoroquinolones may be susceptible to levofloxacin.
Antimicrobial activity: Levofloxacin is often bactericidal at concentrations equal to or slightly greater than inhibitory concentrations. Levofloxacin has been shown to be active against a wide range of Gram-negative and Gram-positive microorganisms both in vitro and in clinical infections as described as follows.
Aerobic Gram-Positive Microorganisms: Enterococcus faecalis, Staphylococcus aureus (methicillin-susceptible strains), Staphylococcus epidermidis (methicillin-susceptible strains), Staphylococcus saprophyticus, Streptococcus pneumoniae (including multi-drug resistant strains), Streptococcus pyogenes.
Aerobic Gram-Negative Microorganisms: Enterobacter cloacae, Escherichia coli, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumonia, Legionella pneumophila, Moraxella catarrhalis, Proteus mirabilis, Pseudomonas aeuriginosa, Serratia marcescens.
Other Microorganisms: Chlamydophila pneumonia, Mycoplasma pneumonia.