Levox Mechanism of Action

Antibacterial.
Pharmacology: Mechanism of Action: Levofloxacin is a synthetic broad spectrum fluoroquinolone for oral and intravenous administration. It is the S (-) enantiomer of the racemic drug, Ofloxacin. Levofloxacin acts on the DNA-DNA gyrase complex and topoisomerase IV.
750 mg Infusion: 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: Bioavailability: Levofloxacin pharmacokinetics are linear and predictable after single and multiple oral/or i.v. dosing regimens. Steady-state conditions are reached within 48 hours following a 500 mg or 750 mg once daily dosage regimen. The mean + SD peak and trough plasma concentrations attained following multiple once-daily oral dosage regimens were approximately 5.7 + 1.4 and 0.5 + 0.2 ug/mL after the 500 mg doses, and 8.6 + 1.9 and 1.1 + 0.4 ug/mL after the 750 mg doses, respectively. The mean + SD peak and trough plasma concentrations attained following multiple once-daily i.v. regimens were approximately 6.4 + 0.8 and 0.6 + 0.2 ug/mL after the 500 mg doses, and 12.1 + 4.1 and 1.3 + 0.71 ug/mL after the 750 mg doses, respectively. Plasma concentration profiles for Levofloxacin I.V. and Levofloxacin oral are nearly superimposable in the post-peak, distribution-elimination phase. Absolute bioavailability after oral administration is almost 100% and approximates that of intravenous administration.
Levofloxacin distributes rapidly throughout the body, achieving concentrations in lung, sputum, otorhinolaryngeal, prostatic and gynecologic tissues and in bronchoalveolar, lacrimal, intraocular, inflammatory and spinal fluids, delivering drug concentrations that greatly exceed MICs of major pathogens.
Levofloxacin is metabolized to a very small extent (< 5%); the metabolites being desmethyl-levofloxacin and levofloxacin N-oxide. Levofloxacin, following oral and intravenous administration, is eliminated relatively slowly from the plasma (t½ of 6 to 8 h), thereby allowing once-daily dosing. Excretion is primarily by the renal route (> 85% of the administered dose).
750 mg Infusion: Levofloxacin pharmacokinetics are linear and predictable after single and multiple oral/intravenous (IV) dosing regimens. Steady-state conditions are reached within 48 hours after a 500 mg or 750 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.
The mean volume of distribution generally ranges from 74 to 112 L after single and multiple 500 mg or 750 mg doses, indicating widespread distribution into body tissues. Penetration of levofloxacin in skin tissues and in blister fluid is rapid and extensive. It also penetrates well into lung tissues. Protein binding is approximately 24% to 38% and is independent of drug concentration.
Levofloxacin is stereochemically stable in plasma and urine and undergoes limited metabolism in humans with less than 5% of an administered dose recovered in the urine.
Plasma half-life (t_1/2) ranges from approximately 6 to 8 hours. The mean apparent total body clearance and renal clearance range from approximately 144 to 226 mL/min and 96 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.
Microbiology: Spectrum of Activity: Levofloxacin is active against a wide spectrum of Gram-positive and Gram-negative microorganisms. Levofloxacin is often bactericidal at concentrations equal to or slightly greater than inhibitory concentrations.
Resistance to Levofloxacin due to spontaneous mutation in vitro is a rare occurrence (range: 10-9 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.
750 mg Infusion: Levofloxacin has been shown to be active against most strains of the following microorganisms both in vitro and in clinical infections: See Table 1.

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Levofloxacin has been shown to be active in vitro against most strains of the following organisms; however, the clinical significance of these data is unknown: See Table 2.

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It is suggested to carry out susceptibility tests.