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

CLINICAL PHARMACOLOGY

Absorption
Levofloxacin is rapidly and essentially completely absorbed after oral administration. Peak plasma concentrations are usually attained one to tow hours after oral dosing. The absolute bioavailability of a 500 mg oral dose of levofloxacin is approximately 99%. Levofloxacin pharmacokinetics are linear and predictable after single and multiple oral dosing regimens. Steady-state is reached within 48 hours 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 hour 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 to 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 to 11.3 mcg/ml over a 24-hour period after a single dose of 500 mg oral dose.

In vitro, over a clinically relevant range (1 to 10 mcg/ml) of serum/plasma levofloxacin concentrations, levofloxacin is approximately 24 to 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 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 give orally or intravenously. The mean apparent total body clearance and renal clearance range from approximately 144 to 226 ml/min and 95 to 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.

Special Populations
Geriatric: There are no significant differences in levofloxacin pharmacokinetics between young and elderly subjects' when the subjects differences in creatinine clearance are taken into consideration. Following a 500 mg oral dose levofloxacin to healthy elderly subjects (66-80 years of age), the mean terminal plasma elimination half-life of levofloxacin was about 7.6 hours, as compared to approximately 6 hours in younger adults. The difference was attributable to the variation in renal function status of the subjects and was not believed to be clinically significant. Drug absorption appears to be unaffected by age. Levofloxacin dose adjustment based on age alone is not necessary.

Pediatric: The pharmacokinetics of levofloxacin in pediatric subjects have not been studied.
Aerobic gram-positive microorganisms:

Staphylococcus epidermidis
Streptococcus (Group C/F)
Streptococcus (Group G)
Staphylococcus saprophyticus
Streptococcus agalactiae
Viridans groupstreptococci

Aerobic gram-negative microorganisms:

Acinetobacter anitratus
Acinetobacter baumannii
Acinetobacter calcoaceticus
Acinetobacter lwofffii
Bordetella pertussis
Citrobacter diversus
Citrobacter freundii
Enterobacter aerogenes
Enterobacter agglomerans
Enterobacter sakazakii
Klebsiella oxytoca
Morganella morganii
Proteus vulgaris
Providencia rettgeri
Providencia stuartii
Pseudomonas fluorascens
Serratia marcescens

Anaerobic gram-positive microorganisms:
Clostridium perfringens

Susceptibility Tests
Susceptibility testing for levofloxacin should be performed as it is the optimal predictor of activity. However, until levofloxacin susceptibility testing is available, the susceptibility of the organism to ofloxacin may be used to predict susceptibility to levofloxacin. While ofloxacin susceptible organisms will be susceptible to levofloxacin, ofloxacin intermediate or resistant organisms may be susceptible to levofloxacin.

Dilution Techniques: Quantitative methods are used to determine antimicrobial minimal inhibitory concentrations (MICs). These provide estimates of the susceptibility of bacteria to antimicrobial compounds. The MICs should be determined using a standardized procedure. Standardized procedures are based on a dilution method1 (broth or agar) or equivalent with standardized inoculum concentrations and standardized concentrations of levofloxacin powder. The MIC values should be interpreted according to the criteria shown in TABLE 1, TABLE 2, and TABLE 3.

The current absence of data on resistant strains precludes defining any categories other than "Susceptable". Strains yielding MIC results suggestive of a "nonsusceptible" category should be submitted to a reference laboratory for further testing.

A report of "Susceptible" indicated that the pathogen is likely to be inhibited if the antimicrobial compound in the blood reaches the concentrations usually achievable. A report of "Intermediate" indicates that the result should be considered equivocal, and if the microorganism is not fully susceptible to alternative, clinically feasible drugs, the test should be repeated. This category implies possible clinical applicability in body sites where the drug is physiologically concentrated or in situations where a high dosage of drug can be used. This category also provides a buffer zone which prevents small uncontrolled technical factors from causing major discrepancies in interpretation. A report of "Resistant" indicates that the pathogen is not likely to be inhibited if the anitmicrobial compound in the blood reaches the concentrations usually achievable: other therapy should be selected.

Standardized susceptibility test procedures require the use of laboratory control microorganisms to control the technical apsects of the laboratory procedures.
Standard Levofloxacin powder should give the following MIC values shown in TABLE 4.

Diffusion Techniques: Quantitative methods that require measurement of zone diameters also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. One such standardized procedure2 requires the use of standardized inoculum concentrations. This procedure uses paper disks impregnated with 5 mcg levofloxacin to test the susceptibility of microorganisms to levofloxacin.

Reports from the laboratory providing results of the standard single-disk susceptibility test with a 5 mcg levofloxacin disk should be interpreted according to the following criteria shown in TABLE 5, TABLE 6, and TABLE 7.

The current absence of data on resistant strains precludes defining any catgories other than "Susceptible". Strains yielding zone diameter results suggestive of a "nonsusceptible" category should be submitted to a reference laboratory for further testing.

Interpretation should be as stated above for results using dilution techniques. Interpretation involves correlation of the diameter obtained in the disk test with the MIC for levofloxacin.

As with standardized dilution techniques, diffusion methods require the use of laboratory control microorganisms to control the technical aspects of the laboratory procedures. For the diffusion technique, the 5 mcg levofloxacin disk should provide the following zone diameters shown in TABLE 8 in these laboratory test quality control strains.

NEXT >>