100986-85-4

Description

Levofloxacin, the optically active S-isomer of the fluoroquinolone antibiotic ofloxacin, is two to four times more potent than ofloxacin with reportedly less side effects in treating infections of the lower respiratory and urinary tract, prostate infections and sexually transmitted diseases. It has broad and potent antibacterial activity over common Grampositive and -negative aerobic pathogens and obligate anaerobes. Different from the cephem antibiotics, levofloxacin is unique in its marked selectivity against members of the family Enterobacteriaceae and its negligible effect on predominant anaerobes. Levofloxacin also exhibits satisfactory antimicrobial effects in surgical infections and it may be used for treatment of gastrointestinal infections such as traveler’s diarrhea associated with the pathogenic Enterobacteriaceae.

Chemical Properties

Slight yellow powder

Originator

Daiichi (Japan)

Uses

Levofloxacin belongs to the class of medicines known as quinolone antibiotics. It works by killing bacteria or preventing their growth. Levofloxacin is active against Gram-positive and Gram-negative bacteria. It inhibits DNA gyrase (type II topoisomerase) and topoisomerase IV, thereby inhibiting cell division.

Brand name

Iquix (Sanofi Winthrop); Levaquin (Ortho-McNeil); Quixin (Sanofi Winthrop);Cravit.

Therapeutic Function

Antibacterial

Pharmaceutical Applications

For molecular weight and structure, see ofloxacin . Levofloxacin is the l-isomer of ofloxacin.

Pharmacokinetics

Oral absorption: >95% Cmax 500 mg oral: c. 5 mg/L after 1.5–2 h 750 mg oral: c. 8 mg/L after 1.5–2 h 500 mg intravenous (90-min infusion): c. 6 mg/L end infusion 750 mg intravenous (90-min infusion) ：c. 12 mg/L end infusion Plasma half-life ：6–8 h Volume of distribution：0.6–0.8 L/kg Plasma protein binding： <25%Co-administration with antacids, calcium, sucralfate and heavy metals decreases bioavailability and AUC. No interactions with warfarin or theophylline have been observed. Co-administration of a non-steroidal anti-inflammatory drug may increase the risk of convulsions. It undergoes limited metabolism and is primarily eliminated unchanged in urine by both glomerular filtration and tubular secretion. The free AUC:MIC ratio for Str. pneumoniae increases from about 55 to 70 when the daily dosage is raised from 500 mg to 750 mg.It is stable in plasma and does not revert to d-ofloxacin. It undergoes limited metabolism and is primarily eliminated unchanged in the urine. Renal clearance in excess of the glomerular filtration rate suggests that tubular secretion also occurs. Concomitant administration of either cimetidine or probenecid reduces renal clearance by approximately onethird. Clearance is reduced and half-life is prolonged in patients with impaired renal function (creatinine clearance <50 mL/min) requiring dosage adjustment in such patients.

Side effects

Side effects have been reported in 6–7% of patients and include fever, rash and other events common to the group. Elderly patients are at increased risk of developing severe tendon disorders including rupture, a risk increased by concomitant corticosteroid therapy.

Metabolism

Levofloxacin is metabolised to a very small extent, the metabolites being desmethyl-levofloxacin and levofloxacin N-oxide. These metabolites account for <5% of the dose and are excreted in urine. Excretion is primarily by the renal route