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Pharmacology: Pharmacodynamics: Levofloxacin is the L-isomer of the racemate, ofloxacin, a quinolone antibacterial agent. The mechanism of action of levofloxacin and other quinolones involves inhibition of bacterial topoisomerase II (DNA gyrase) and topoisomerase IV enzymes which are essential for DNA replication, transcription, repair, and recombination.
Pharmacokinetics: Levofloxacin pharmacokinetics are linear and predictable after single and multiple oral/intravenous (IV) dosing regimens. It is rapidly and almost completely absorbed after oral doses with peak plasma concentrations occurring within 1 to 2 hours. Food has little effect on the absorption of levofloxacin. Steady-state conditions are reached within 48 hours after a 500 mg once daily dosage regimen. The oral and IV route of administration may also be considered interchangeable since levofloxacin's plasma concentration profiles are nearly superimposable in the post-peak, distribution-elimination phase.
Levofloxacin is widely distributed into body tissues including the bronchial mucosa and lungs, but penetration into the cerebrospinal fluid is relatively poor. The mean volume of distribution of levofloxacin is approximately 100 L after single and repeated doses. Protein binding is about 30 to 40%.
Levofloxacin is metabolized to a very small extent, the metabolites being desmethyl-levofloxacin and levofloxacin N-oxide. These metabolites account for <5% of the dose excreted in urine. Levofloxacin is stereochemically stable and does not undergo chiral inversion.
The elimination half-life of the drug is 6 to 8 hours, although this may be prolonged in patients with renal impairment. Levofloxacin is excreted largely unchanged, primarily in the urine with less than 5% as metabolites. It is not removed by hemodialysis or peritoneal dialysis.
Special Population: Renal Impairment: Clearance of levofloxacin is reduced and plasma elimination half-life is prolonged in patients with impaired renal function (creatinine clearance ≤80 mL/min). Dosage adjustment may be required to avoid accumulation.
Hepatic Impairment: Due to the limited extent of levofloxacin metabolism, the pharmacokinetics of levofloxacin are not expected to be affected by hepatic impairment.
Geriatrics: There are no significant differences in levofloxacin pharmacokinetics between the young and elderly subjects when the subjects' differences in creatinine clearance are taken into consideration. Drug absorption appears to be unaffected by age. Dose adjustment based on age is not necessary.
Microbiology: Antimicrobial Spectrum of Activity: Levofloxacin has been shown to be active against most strains of the following microorganisms both in vitro and in clinical infections: see Table 1.
Click on icon to see table/diagram/imageLevofloxacin has been shown to be in active in vitro against most strains of the following organisms; however, the clinical significance of these data is unknown: see Table 2.
Click on icon to see table/diagram/image