Pharmacological properties
Pharmacodynamics. Levofloxacin - the l-isomer of racemates, ofloxacin, a quinolone antibiotic - is characterized by a wide spectrum of antibacterial action. The bactericidal effect is provided by the inhibition of the bacterial enzyme DNA gyrase by levofloxacin, which belongs to type II topoisomerases. The result of such inhibition is the inability of bacterial DNA to transition from a relaxed state to a supercoiled state, which, in turn, makes further division (reproduction) of bacterial cells impossible. The spectrum of activity of levofloxacin includes gram-positive and gram-negative bacteria, along with non-fermenting bacteria.
The following microorganisms are sensitive to the drug:
gram-positive aerobes
Enterococcus faecalis (moderately sensitive), Staphylococcus aureus (methicillin strains), Staphylococcus saprophyticus, Streptococci, group C and G, Streptococcus agalactiae, Streptococcus pneumoniae (including penicillin strains), Streptococcus pyogenes.
gram-negative aerobes
Burkholderia cepacia, Eikenella corrodens, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella oxytoca, Klebsiella pneumoniae, Moraxella catarrhalis, Pasteurella multocida, Proteus vulgaris, Providencia rettgeri.
anaerobes
Peptostreptococcus.
others
Chlamydia pneumoniae, Mycoplasma pneumoniae, Chlamydia psittacci, Chlamydia trachomatis, Legionella pneumophila, Mycoplasma hominis, Ureaplasma urealyticum.
Microorganisms to which sensitivity may develop
gram-positive aerobes
Enterococcus faecalis, Staphylococcus aureus (methicillin strains), Coagulase negative Staphylococcus spp.
gram-negative aerobes
Escherichia coli, Enterobacter cloacae, Salmonella Species, Proteus mirabilis, Pseudomonas aeruginosa, Acinetobacter baumanii, Citrobacter freundii, Enterobacter aerogenes, Enterobacter agglomerans, Morganella morganii, Providencia stuartii, Serratia marcescens.
anaerobic bacteria
Bacteroides fragilis, Bacteroides ovatus, Bacteroides thetaiotaomicron, Bacteroides vulgatus, Clostridium difficile.
Pharmacokinetics. Absorption. Orally administered levofloxacin is rapidly and almost completely absorbed; C max in blood plasma is reached 1-2 hours after administration. Bioavailability is almost 100%. Food intake slightly affects its absorption.
Distribution. Approximately 30-40% of levofloxacin is bound to plasma proteins. The cumulative effect of levofloxacin at a dosage of 500 mg once daily is not clinically significant and can be neglected. There is a slight but predictable accumulation at a dosage of 500 mg twice daily. Stabilization is achieved after 3 days of use.
Penetration into tissues and body fluids. Penetration into bronchial mucus, epithelial fluid. C max of levofloxacin in bronchial mucus, bronchoalveolar lavage fluid after administration of 500 mg is 8.2 and 10.8 mg / g, respectively, and is achieved 1 hour after administration.
Penetration into lung tissue. C max of levofloxacin in lung tissue after administration of 500 mg is approximately 11.3 mg/g and is reached 4-6 hours after administration. The concentration of levofloxacin in lung tissue significantly exceeds its concentration in blood plasma.
Penetration into the contents of the urinary bladder. C max of levofloxacin in the contents of the urinary bladder after administration of 500 mg 1-2 times a day for 3 days is approximately 4.0-6.7 mg / g and is achieved 2-4 hours after administration.
Penetration into cerebrospinal fluid. Almost non-penetrating.
Penetration into prostate tissue. The average concentration of levofloxacin in prostate tissue after administration of 500 mg 1 time per day for 3 days is 8.7; 8.2 and 2 mg / g and is achieved 2; 6 and 24 hours after administration, respectively.
Urine concentration. The average concentration of levofloxacin in urine after administration of 150; 300 or 500 mg 1 time per day is 44; 91 and 200 mg/l, respectively, and is reached 8-12 hours after administration.
Metabolism: Levofloxacin is metabolized to a very small extent, the metabolites are desmethyl-levofloxacin and levofloxacin-N-oxide. These metabolites constitute less than 5% of the drug.
Elimination. After oral administration, levofloxacin is eliminated from plasma relatively slowly (T½ is 6-8 hours). Excretion is mainly by the kidneys (85% of the administered dose). There is no significant difference in the pharmacokinetics of levofloxacin after intravenous and oral administration.
Levofloxacin has linear pharmacokinetics from 50 to 600 mg.
Patients with renal insufficiency. The pharmacokinetics of levofloxacin depends on renal function. With a decrease in renal excretion and clearance, T ½ increases.
The pharmacokinetics of levofloxacin depend on renal function. With a decrease in renal excretion and clearance, T½ increases.
| Clcr, ml/min | 20 | 20-40 | 50-80 |
| ClR, ml/min | 13 | 26 | 57 |
| T ½, h | 35 | 27 | 9 |
|
Elderly patients. The pharmacokinetics of levofloxacin do not differ between young and elderly patients, except for differences in clearance.
