Levobact Mechanism of Action

Antimicrobial fluoroquinolone.
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 topoisomerase II), an enzyme required for DNA replication, 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 β-lactam antibiotics. Fluoroquinolones may, therefore, be active against bacteria resistant to β-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 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 catarrhalis, Proteus mirabilis, Pseudomonas aeruginosa; other microorganisms: Chlamydia pneumoniae, Mycoplasma pneumoniae.
Pharmacokinetics: Absorption: Levofloxacin is rapidly, essentially and completely absorbed after oral administration. Peak plasma concentrations are usually attained 1-2 hrs after oral dosing. The absolute bioavailability of a 500-mg oral dose of levofloxacin is approximately 99%. Levofloxacin pharmacokinetics is linear and predictable after single and multiple oral dosing regimens. Steady state is reached within 48 hrs following a 500-mg once daily regimen. The peak and trough plasma concentrations attained following multiple once daily oral 500-mg regimens were approximately 5.7 and 0.5 mcg/mL, respectively. Oral administration with food slightly prolongs the time to peak concentration by approximately 1 hr and slightly decreases the peak concentration by approximately 14%. Therefore, levofloxacin can be administered without regard to food. The plasma concentration profile of levofloxacin after IV administration is similar and comparable in extent of exposure (AUC) to that observed for levofloxacin tablets when equal doses (mg/mg) are administered. Therefore, the oral and IV routes of administration can be considered interchangeable.
Distribution: The mean volume of distribution of levofloxacin generally ranges from 89-112 L after single and multiple 500-mg doses, indicating widespread distribution into body tissues. Penetration of levofloxacin into blister fluid is rapid and extensive. The blister fluid to plasma AUC ratio is approximately 1. Levofloxacin also penetrates well into lung tissues. Lung tissue concentrations were generally 2- to 5-fold higher than plasma concentrations and ranged from approximately 2.4-11.3 mcg/mL over a 24-hr period after a single dose of 500-mg oral dose. In vitro, over a clinically relevant range (1-10 mcg/mL) of serum/plasma levofloxacin concentrations, levofloxacin is approximately 24-38% bound to serum proteins across all species studied, as determined by the equilibrium dialysis method. Levofloxacin is mainly bound to serum albumin in humans. Levofloxacin binding to serum proteins is independent of the drug concentration.
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 urine. Following oral administration, approximately 87% of an administered dose was recovered as unchanged drug in urine within 48 hrs, whereas <4% of the dose was recovered in feces in 72 hrs. 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 6-8 hrs following single or multiple doses of levofloxacin given orally or IV. The mean apparent total body clearance and renal clearance range from approximately 144-226 mL/min and 95-142 mL/min, respectively. Renal clearance in excess of the glomerular filtration rate suggests that tubular secretion of levofloxacin occurs in addition to its glomerular filtration. Concomitant administration of either cimetidine or probenecid results in approximately 24% and 35% reduction in the levofloxacin renal clearance, respectively, indicating that secretion of levofloxacin occurs in the renal proximal tubule. No levofloxacin crystals were found in any of the urine samples freshly collected from subjects receiving levofloxacin.